2,715 results on '"Cytochalasins"'
Search Results
2. Novel Metabolites from the Marine-Derived Fungus Peniophora sp. SCSIO41203 Show Promising In Vitro Antitumor Activity as Methuosis Inducers in PC-3 Cells.
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Yang, Bin, Shao, Surun, Nie, Mingyi, Tie, Qingqing, Pang, Xiaoyan, Lin, Xiuping, Zhou, Xuefeng, Liu, Yonghong, Wang, Xueni, and Li, Yunqiu
- Abstract
Two new cytochalasin derivatives, peniotrinins A (1) and B (2), three new citrinin derivatives, peniotrinins C–E (4, 5, 7), and one new tetramic acid derivative, peniotrinin F (12), along with nine structurally related known compounds, were isolated from the solid culture of Peniophora sp. SCSIO41203. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis, quantum chemical calculations, and the calculated ECD. Interestingly, 1 is the first example of a rare 6/5/5/5/6/13 hexacyclic cytochalasin. We screened the above compounds for their anti-prostate cancer activity and found that compound 3 had a significant anti-prostate cancer cell proliferation effect, while compounds 1 and 2 showed weak activity at 10 μM. We then confirmed that compound 3 exerts its anti-prostate cancer effect by inducing methuosis through transmission electron microscopy and cellular immunostaining, which suggested that compound 3 might be first reported as a potential anti-prostate methuosis inducer. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Cytochalasins as Modulators of Stem Cell Differentiation.
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Pampanella, Luca, Petrocelli, Giovannamaria, Abruzzo, Provvidenza Maria, Zucchini, Cinzia, Canaider, Silvia, Ventura, Carlo, and Facchin, Federica
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CYTOCHALASINS , *CELL differentiation , *STEM cells , *MESENCHYMAL stem cells , *REGENERATIVE medicine - Abstract
Regenerative medicine aims to identify new research strategies for the repair and restoration of tissues damaged by pathological or accidental events. Mesenchymal stem cells (MSCs) play a key role in regenerative medicine approaches due to their specific properties, such as the high rate of proliferation, the ability to differentiate into several cell lineages, the immunomodulatory potential, and their easy isolation with minimal ethical issues. One of the main goals of regenerative medicine is to modulate, both in vitro and in vivo, the differentiation potential of MSCs to improve their use in the repair of damaged tissues. Over the years, much evidence has been collected about the ability of cytochalasins, a large family of 60 metabolites isolated mainly from fungi, to modulate multiple properties of stem cells (SCs), such as proliferation, migration, and differentiation, by altering the organization of the cyto- and the nucleo-skeleton. In this review, we discussed the ability of two different cytochalasins, cytochalasins D and B, to influence specific SC differentiation programs modulated by several agents (chemical or physical) or intra- and extra-cellular factors, with particular attention to human MSCs (hMSCs). [ABSTRACT FROM AUTHOR]
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- 2024
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4. Novel Metabolites from the Marine-Derived Fungus Peniophora sp. SCSIO41203 Show Promising In Vitro Antitumor Activity as Methuosis Inducers in PC-3 Cells
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Bin Yang, Surun Shao, Mingyi Nie, Qingqing Tie, Xiaoyan Pang, Xiuping Lin, Xuefeng Zhou, Yonghong Liu, Xueni Wang, and Yunqiu Li
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marine fungus ,Peniophora sp. ,cytochalasins ,citrinin ,peniotrinin ,anti-prostate methuosis inducer ,Biology (General) ,QH301-705.5 - Abstract
Two new cytochalasin derivatives, peniotrinins A (1) and B (2), three new citrinin derivatives, peniotrinins C–E (4, 5, 7), and one new tetramic acid derivative, peniotrinin F (12), along with nine structurally related known compounds, were isolated from the solid culture of Peniophora sp. SCSIO41203. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis, quantum chemical calculations, and the calculated ECD. Interestingly, 1 is the first example of a rare 6/5/5/5/6/13 hexacyclic cytochalasin. We screened the above compounds for their anti-prostate cancer activity and found that compound 3 had a significant anti-prostate cancer cell proliferation effect, while compounds 1 and 2 showed weak activity at 10 μM. We then confirmed that compound 3 exerts its anti-prostate cancer effect by inducing methuosis through transmission electron microscopy and cellular immunostaining, which suggested that compound 3 might be first reported as a potential anti-prostate methuosis inducer.
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- 2024
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5. Phoma spp. an untapped treasure of cytotoxic compounds: current status and perspectives.
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Rai, Mahendra, Zimowska, Beata, Gade, Aniket, and Ingle, Pramod
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PHOMA , *METABOLITES , *BIOACTIVE compounds , *CYTOCHALASINS , *ANTINEOPLASTIC agents , *NEMATOCIDES - Abstract
The genus Phoma has been explored for a wide range of secondary metabolites signifying a huge range of bioactivities. Phoma sensu lato is a major group that secretes several secondary metabolites. The genus Phoma mainly includes Phoma macrostoma, P. multirostrata, P. exigua, P. herbarum, P. betae, P. bellidis, P. medicaginis, P. tropica, and many more species from the genus that are continuously being identified for their potential secondary metabolites. The metabolite spectrum includes bioactive compounds like phomenon, phomin, phomodione, cytochalasins, cercosporamide, phomazines, and phomapyrone reported from various Phoma spp. These secondary metabolites show a broad range of activities including antimicrobial, antiviral, antinematode, and anticancer. The present review is aimed to emphasize the importance of Phoma sensu lato fungi, as a natural source of biologically active secondary metabolites, and their cytotoxic activities. So far, cytotoxic activities of Phoma spp. have not been reviewed; hence, this review will be novel and useful for the readers to develop Phoma-derived anticancer agents. Key points: • Different Phoma spp. contain a wide variety of bioactive metabolites. • These Phoma spp. also secrete cytotoxic and antitumor compounds. • The secondary metabolites can be used for the development of anticancer agents. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Cytochalasins as Modulators of Stem Cell Differentiation
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Luca Pampanella, Giovannamaria Petrocelli, Provvidenza Maria Abruzzo, Cinzia Zucchini, Silvia Canaider, Carlo Ventura, and Federica Facchin
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cytochalasins ,stem cells ,mesenchymal stem cells ,mesenchymal stromal cells ,actin microfilaments ,cytoskeleton ,Cytology ,QH573-671 - Abstract
Regenerative medicine aims to identify new research strategies for the repair and restoration of tissues damaged by pathological or accidental events. Mesenchymal stem cells (MSCs) play a key role in regenerative medicine approaches due to their specific properties, such as the high rate of proliferation, the ability to differentiate into several cell lineages, the immunomodulatory potential, and their easy isolation with minimal ethical issues. One of the main goals of regenerative medicine is to modulate, both in vitro and in vivo, the differentiation potential of MSCs to improve their use in the repair of damaged tissues. Over the years, much evidence has been collected about the ability of cytochalasins, a large family of 60 metabolites isolated mainly from fungi, to modulate multiple properties of stem cells (SCs), such as proliferation, migration, and differentiation, by altering the organization of the cyto- and the nucleo-skeleton. In this review, we discussed the ability of two different cytochalasins, cytochalasins D and B, to influence specific SC differentiation programs modulated by several agents (chemical or physical) or intra- and extra-cellular factors, with particular attention to human MSCs (hMSCs).
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- 2024
- Full Text
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7. Six Unprecedented Cytochalasin Derivatives from the Potato Endophytic Fungus Xylaria curta E10 and Their Cytotoxicity.
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Zhang, Xian, Fan, Yinzhong, Ye, Ke, Pan, Xiaoyan, Ma, Xujun, Ai, Honglian, Shi, Baobao, and Liu, Jikai
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ENDOPHYTIC fungi , *XYLARIA , *CYTOCHALASINS , *CIRCULAR dichroism , *POTATOES , *CELL lines , *ANTIBODY-dependent cell cytotoxicity - Abstract
Six previously undescribed cytochalasins, Curtachalasins X1–X6 (1–6), together with six known compounds (7–12) were isolated from the endophytic fungus Xylaria curta E10 harbored in the plant Solanum tuberosum. The structures were elucidated by the interpretation of HRESIMS, UV, and NMR data. The absolute configurations of Curtachalasins X1–X6 were determined by comparison of their experimental and calculated electronic circular dichroism (ECD) spectra. In bioassays, Curtachalasin X1 (1) and X5 (5) showed cytotoxic activity against the MCF-7 cell line with IC50 values of 2.03 μM and 0.85 μM, respectively. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Molecular docking study of Cytochalasin H and Fascin interactions as prospective targets for gastric cancer.
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Heidarzadeh, Samaneh and Ashrafmansouri, Seyedeh-Samira
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MOLECULAR docking ,CYTOCHALASINS ,MICROFILAMENT proteins ,STOMACH cancer ,PROTEIN-drug interactions - Abstract
Background: Gastric cancer is the fifth most common neoplasm and the fourth leading cause of mortality worldwide. Incidence rates vary widely and depend on risk factors, epidemiological factors, and carcinogenesis patterns. Understanding the molecular mechanisms underlying cancer progression and metastasis is crucial for developing effective therapeutic strategies. Previous studies have reported that fascin overexpression, an actin-binding protein, promotes cell motility and invasion in cancers by bundling actin filaments. Therefore, inhibiting this protein can be a major step in treatment. Methods: In this prospective study, the protein structure of fascin was obtained from the Protein Data Bank (PDB). Using the HyperChem 7.0 software, the chemical structure of cytochalasin H as a small molecule inhibitor was designed. Rigid docking studies between cytochalasin H and fascin protein were performed using the AutoDock Vina 1.1.2 software, and the obtained results were analyzed using LigPlot+ v.1.4.5, Discovery Studio 4.5, and PyMOL v.1.9 software. Results: According to the analyses and the obtained results, cytochalasin H and fascin protein have an effective interaction with an optimal energy level. Conclusion: These findings suggest that cytochalasin H may be developed into a potential chemotherapeutic drug for the treatment of gastric cancer by inhibiting fascin. Nevertheless, further in vitro and in vivo experiments are necessary to elucidate the exact mechanism. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Cytochalasins from the Endophytic Fungus Fusarium sp. GDGJ-366.
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Huang, Li-Li, Xu, Zhao-Long, Liang, Min, Lv, Liu-Xia, Li, Ben-Chao, Qin, Xiao-Ya, Huang, Xi-Shan, Li, Jun, Xu, Wei-Feng, and Yang, Rui-Yun
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CYTOCHALASINS , *FUSARIUM , *NORMAL-phase chromatography - Abstract
4.3 (400.0 mg) which was purified by Sephadex LH-20 (MeOH-H SB 2 sb O, 5:5) and semipreparative HPLC (CH SB 3 sb CN-H SB 2 sb O, 11:9). SP 1 sp H NMR (400 MHz, CDCl SB 3 sb , , ppm, J/Hz): 7.06 (2H, d, J = 8.4, H-2', 6'), 6.85 (2H, d, J = 8.4, H-3', 5'), 6.48 (1H, d, J = 11.6, H-20), 5.88 (1H, ddd, J = 15.0, 9.9, 2.2, H-13), 5.60 (1H, d, J = 11.6, H-19), 5.21 (1H, ddd, J = 15.0, 10.9, 3.8, H-14), 4.38 (1H, br.s, H-7), 3.77 (3H, s, 4'-OCH SB 3 sb ), 3.70 (1H, m, H-3), 2.99 (1H, dd, J = 5.2, 2.6, H-4), 2.93 (1H, ddd, J = 11.6, 6.8, 2.2, H-16), 2.83 (1H, dd, J = 13.7, 4.6, H-10a), 2.65 (1H, d, J = 4.6, H-10b), 2.62 (1H, overlapped, H-15a), 2.60 (1H, overlapped, H-8), 2.27 (1H, dd, J = 7.4, 5.2, H-5), 2.14 (1H, m, H-15b), 1.47 (3H, s, H-23), 1.25 (3H, s, H-12), 1.15 (3H, d, J = 6.8, H-22), 1.08 (3H, d, J = 7.4, H-11). SP 1 sp H NMR (400 MHz, DMSO-d SB 6 sb , , ppm): 9.19 (1H, s, 2-NH), 8.08 (1H, s, 4'-OH), 6.95 (2H, d, J = 8.4, H-2', 6'), 6.67 (2H, d, J = 8.4, H-3', 5'), 6.33 (1H, d, J = 12.7, H-20), 5.60 (1H, overlapped, H-19), 5.57 (1H, overlapped, H-13), 5.33 (1H, ddd, J = 15.2, 10.8, 4.3, H-14), 5.26 (1H, d, J = 2.2, H-7), 4.03 (1H, q, J = 7.1, H-3), 3.32 (1H, m, H-18), 2.93 (1H, m, H-4), 2.88 (1H, d, J = 9.2, H-8), 2.74 (2H, m, H-10), 2.71 (1H, m, H-16), 2.68 (1H, m, H-5), 2.46 (1H, m, H-15a), 2.03 (1H, m, H-15b), 1.67 (3H, s, H-12), 1.16 (3H, d, J = 6.9, H-22), 1.11 (3H, d, J = 6.8, H-23), 0.70 (3H, d, J = 7.2, H-11). [Extracted from the article]
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- 2023
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10. Identification of natural cytochalasins as leads for neglected tropical diseases drug discovery.
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Valli, Marilia, Souza, Julia Medeiros, Chelucci, Rafael Consolin, Biasetto, Carolina Rabal, Araujo, Angela Regina, Bolzani, Vanderlan da Silva, and Andricopulo, Adriano Defini
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NEGLECTED diseases , *CYTOCHALASINS , *DRUG discovery , *ANTIPARASITIC agents , *CHAGAS' disease , *FUNGAL metabolites - Abstract
Investigating the chemical diversity of natural products from tropical environments is an inspiring approach to developing new drug candidates for neglected tropical diseases (NTDs). In the present study, phenotypic screenings for antiprotozoal activity and a combination of computational and biological approaches enabled the identification and characterization of four cytochalasins, which are fungal metabolites from Brazilian biodiversity sources. Cytochalasins A-D exhibited IC50 values ranging from 2 to 20 μM against intracellular Trypanosoma cruzi and Leishmania infantum amastigotes, values comparable to those of the standard drugs benznidazole and miltefosine for Chagas disease and leishmaniasis, respectively. Furthermore, cytochalasins A-D reduced L. infantum infections by more than 80% in THP-1 cells, most likely due to the inhibition of phagocytosis by interactions with actin. Molecular modelling studies have provided useful insights into the mechanism of action of this class of compounds. Furthermore, cytochalasins A-D showed moderate cytotoxicity against normal cell lines (HFF-1, THP-1, and HepG2) and a good overall profile for oral bioavailability assessed in vitro. The results of this study support the use of natural products from Brazilian biodiversity sources to find potential drug candidates for two of the most important NTDs. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Epigenetic Manipulation Induced Production of Immunosuppressive Chromones and Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48.
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Feng, Ting, Wei, Chengwen, Deng, Xiaolin, Chen, Dandan, Wen, Zhenchang, and Xu, Jing
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A mangrove endophytic fungus Phomopsis asparagi DHS-48 was found to be particularly productive with regard to the accumulation of substantial new compounds in our previous study. In order to explore its potential to produce more unobserved secondary metabolites, epigenetic manipulation was used on this fungus to activate cryptic or silent genes by using the histone deacetylase (HDAC) inhibitor sodium butyrate and the DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-Aza). Based on colony growth, dry biomass, HPLC, and
1 H NMR analyses, the fungal chemical diversity profile was significantly changed compared with the control. Two new compounds, named phaseolorin J (1) and phomoparagin D (5), along with three known chromones (2–4) and six known cytochalasins (6–11), were isolated from the culture treated with sodium butyrate. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD and13 C NMR calculations. The immunosuppressive and cytotoxic activities of all isolated compounds were evaluated. Compounds 1 and 8 moderately inhibited the proliferation of ConA (concanavalin A)-induced T and LPS (lipopolysaccharide)-induced B murine spleen lymphocytes. Compound 5 exhibited significant in vitro cytotoxicity against the tested human cancer cell lines Hela and HepG2, which was comparative to the positive control adriamycin and fluorouracil. Our finding demonstrated that epigenetic manipulation should be an efficient strategy for the induction of new metabolites from mangrove endophytic fungi. [ABSTRACT FROM AUTHOR]- Published
- 2022
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12. Immunosuppressive Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48.
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Feng, Zhao, Zhang, Xuexia, Wu, Jingwan, Wei, Chengwen, Feng, Ting, Zhou, Dongdong, Wen, Zhenchang, and Xu, Jing
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Three new cytochalasins, phomoparagins A-C (1–3), along with five known analogs (4–8), were isolated from Phomopsis asparagi DHS-48, a mangrove-derived endophytic fungus. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD techniques. Notably, 1 possessed an unprecedented 5/6/5/8/5-fused pentacyclic skeleton. These compounds were tested for their inhibitory activity against concanavalin A (ConA)/lipopolysaccharide (LPS)-induced spleen lymphocyte proliferation and calcineurin (CN) enzyme. Several metabolites (2 and 4–6) exhibited fascinating inhibitory activities with a relatively low toxicity. Furthermore, 2 was demonstrated to inhibit ConA-stimulated activation of NFAT1 dephosphorylation and block NFAT1 translocation in vitro, subsequently inhibiting the transcription of interleukin-2 (IL-2). Our results provide evidence that 2 may, at least partially, suppress the activation of spleen lymphocytes via the CN/NFAT signaling pathway, highlighting that it could serve as an effective immunosuppressant that is noncytotoxic and natural. [ABSTRACT FROM AUTHOR]
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- 2022
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13. TRAIL-sensitizing Cytochalasins from the Endophytic Fungus Phoma multirostrata.
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Peng, Xiaogang, Ouyang, Qianxi, Pei, Jiao, Chang, Jinling, Qin, Chunlun, and Ruan, Hanli
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FUNGI classification , *INDOLE compounds , *FUNGI , *MAGNETIC resonance imaging , *APOPTOSIS , *CELL survival , *TUMOR necrosis factors , *MASS spectrometry , *CRYSTALLOGRAPHY , *MOLECULAR structure - Abstract
Seven undescribed cytochalasins, multirostratins K – Q (2 – 8), together with one known analogue, cytochalasin Z3 (1), were isolated from the culture of Phoma multirostrata XJ-2-1, an endophytic fungus obtained from the root of Parasenecio albus. Their structures with absolute configurations were determined by 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), electronic circular dichroism (ECD), single-crystal X-ray crystallography, and chemical methods. The structure of ascochalasin was revised from Δ 13 to Δ 21 by detailed analysis of the NMR data and by comparison with the data for 7. In a TRAIL (tumor necrosis factor related apoptosis inducing ligand)-resistance-overcoming experiment, co-treatment of 2 or 6 with TRAIL reduced the cell viability of A549 cells by 30.3% and 27.5% at 10 µM, respectively. [ABSTRACT FROM AUTHOR]
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- 2022
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14. Six 19,20-epoxycytochalasans from endophytic Diaporthe sp. RJ-47.
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Zhang, Qiong, Huang, Zhi-pu, Zhao, Yu-ying, Zhao, Qing, Chen, Jian-hong, Ma, Wei-guang, and Zhang, Xiao-mei
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ENDOPHYTIC fungi ,CYTOCHALASINS - Abstract
Two new cytochalasins, deacetyl-19-epi-cytochalasin P1 (1), deacetyl-19,20-epoxycytochalasin D (2) were isolated from the endophytic fungus Diaporthe sp. RJ-47, along with four known compounds deacetyl-5,6-dihydro-7-oxo-19,20-epoxycytochalasin C (3), 19,20-epoxycytochalasin Q (4), 19,20-epoxycytochalasin C (5) and deacetyl-19,20-epoxy cytochalasin C (6). Their structures were unambiguously elucidated on the basis of the comprehensive analysis of extensive spectroscopic data. The antimicrobial effects of these compounds were evaluated. [ABSTRACT FROM AUTHOR]
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- 2022
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15. Antiproliferative and Cytotoxic Cytochalasins from Sparticola triseptata Inhibit Actin Polymerization and Aggregation.
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Garcia, Katherine Yasmin M., Quimque, Mark Tristan J., Lambert, Christopher, Schmidt, Katharina, Primahana, Gian, Stradal, Theresia E. B., Ratzenböck, Andreas, Dahse, Hans-Martin, Phukhamsakda, Chayanard, Stadler, Marc, Surup, Frank, and Macabeo, Allan Patrick G.
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POLYKETIDES , *TIME-dependent density functional theory , *CYTOCHALASINS , *ACTIN , *POLYMERIZATION , *STRUCTURE-activity relationships , *MYELOID leukemia - Abstract
Laying the groundwork on preliminary structure–activity relationship study relating to the disruptive activity of cytochalasan derivatives on mammalian cell actin cytoskeleton, we furthered our study on the cytochalasans of the Dothideomycetes fungus, Sparticola triseptata. A new cytochalasan analog triseptatin (1), along with the previously described cytochalasans deoxaphomin B (2) and cytochalasin B (3), and polyketide derivatives cis-4-hydroxy-6-deoxyscytalone (4) and 6-hydroxymellein (5) were isolated from the rice culture of S. triseptata. The structure of 1 was elucidated through NMR spectroscopic analysis and high-resolution mass spectrometry (HR-ESI-MS). The relative and absolute configurations were established through analysis of NOESY spectroscopic data and later correlated with experimental electronic circular dichroism and time-dependent density functional theory (ECD–TDDFT) computational analysis. Compounds 1 and 2 showed cytotoxic activities against seven mammalian cell lines (L929, KB3.1, MCF-7, A549, PC-3, SKOV-3, and A431) and antiproliferative effects against the myeloid leukemia K-562 cancer cell line. Both 1 and 2 were shown to possess properties inhibiting the F-actin network, prompting further hypotheses that should to be tested in the future to enable a well-resolved concept of the structural implications determining the bioactivity of the cytochalasin backbone against F-actin. [ABSTRACT FROM AUTHOR]
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- 2022
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16. New Lung Cancer Study Findings Have Been Reported by Researchers at Chinese Academy of Sciences (Dual Inhibitory Potential of Ganoderic Acid a On Glut1/3: Computational and in Vitro Insights Into Targeting Glucose Metabolism In Human...).
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LUNG tumors ,LUNG cancer ,PHYSICAL sciences ,LUNG diseases ,ARTIFICIAL intelligence ,GLUCOSE transporters - Abstract
Researchers at the Chinese Academy of Sciences have conducted a study on lung cancer, focusing on the potential of ganoderic acid A (GAA) to inhibit glucose metabolism in cancer cells. The study utilized computational modeling, molecular docking, and in vitro experiments to investigate GAA's effects on glucose transporters GLUT1 and GLUT3. The findings suggest that GAA has the ability to bind and stabilize these transporters, leading to a reduction in glucose uptake in lung cancer cells. This research highlights the potential utility of GAA in cancer therapy by targeting glucose metabolism. [Extracted from the article]
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- 2024
17. Actin Polymerization Status Regulates Tendon Homeostasis through Myocardin-Related Transcription Factor-A.
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A preprint abstract from biorxiv.org discusses the regulation of tenocyte homeostasis, specifically focusing on the role of actin polymerization and the myocardin-related transcription factor-a (MRTF). The study found that decreasing the proportion of G-actin in tenocytes through treatment with TGFb1 increased nuclear MRTF and led to favorable alterations in tenocyte gene expression. On the other hand, latrunculin A and cytochalasin D treatments had differing effects on gene expression, suggesting that actin signals through MRTF to regulate a specific subset of genes. Understanding the regulation of tenocyte homeostasis by actin may have implications for developing new therapeutic interventions for tendinopathies. [Extracted from the article]
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- 2024
18. Researchers from Keio University Discuss Findings in Nanotubes (Tunneling nanotube-driven complete regeneration of murine fetal skin).
- Abstract
A recent study conducted by researchers from Keio University explored the role of tunneling nanotubes (TNTs) in the regeneration of fetal mouse skin. The study focused on the spatial relationships between different cell types involved in skin regeneration and the potential impact of TNTs. The researchers found that epidermal keratinocytes interacted with dermal fibroblasts and macrophages, facilitating skin regrowth. TNT structures were observed at the wound sites, indicating their involvement in achieving complete skin texture restoration. This study highlights the importance of 3D cellular interactions during skin regeneration in mouse embryos. [Extracted from the article]
- Published
- 2024
19. Rosellichalasins A–H, cytotoxic cytochalasans from the endophytic fungus Rosellinia sp. Glinf021.
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Gu, Gan, Hou, Xuwen, Xue, Mengyao, Jia, Xiaowei, Pan, Xiaoqian, Xu, Dan, Dai, Jungui, Lai, Daowan, and Zhou, Ligang
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DIELS-Alder reaction , *ENDOPHYTIC fungi , *RING formation (Chemistry) , *GLYCYRRHIZA , *CELL lines , *CANCER cells , *MEDICINAL plants - Abstract
Eight new cytochalasans rosellichalasins A–H (1 – 8), as well as two new shunt metabolites rosellinins A (9) and B (10) before intramolecular Diels–Alder cycloaddition reaction in cytochalasan biosynthesis, along with nine known cytochalsans (11 – 19) were isolated from the endophytic fungus Rosellinia sp. Glinf021, which was derived from the medicinal plant Glycyrrhiza inflata. Their structures were characterized by extensive analysis of 1D and 2D NMR as well as HRESIMS spectra and quantum chemical ECD calculations. The cytotoxic activities of these compounds were evaluated against four human cancer cell lines including HCT116, MDA-MB-231, BGC823, and PANC-1 with IC 50 values ranging from 0.5 to 58.2 μM. Seventeen cytochalasans including eight undescribed ones along with two new shunt metabolites were isolated from the endophytic fungus Rosellinia sp. Glinf021. Some of the isolated compounds exhibited moderate to strong cytotoxic activity. [Display omitted] • Eight new cytochalasans rosellichalasins A–H were isolated from the endophytic fungus Rosellinia sp. Glinf021. • Rosellichalasin A was a rare pyrolidine/perhydroanthracene cytochalasan with a 5/6/6/6 tetracyclic skeleton. • Two shunt metabolites rosellinins A and B in cytochalasan biosynthesis were reported for the first time. • Some of compounds showed in vitro cytotoxic activities against four human cancer cell lines. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Diversified Chaetoglobosins from the Marine-Derived Fungus Emericellopsis sp. SCSIO41202.
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Shao, Surun, Wang, Xueni, She, Jianglian, Zhang, Han, Pang, Xiaoyan, Lin, Xiuping, Zhou, Xuefeng, Liu, Yonghong, Li, Yunqiu, and Yang, Bin
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ACETYLCHOLINESTERASE , *TETRAMIC acids , *ACID derivatives , *CYTOCHALASINS , *DIKETOPIPERAZINES , *FUNGI - Abstract
Two undescribed cytochalasins, emeriglobosins A (1) and B (2), together with nine previously reported analogues (3–11) and two known tetramic acid derivatives (12, 13) were isolated from the solid culture of Emericellopsis sp. SCSIO41202. Their structures, including the absolute configurations of their stereogenic carbons, were fully elucidated based on spectroscopic analysis and the calculated ECD. Some of the isolated compounds were evaluated for their cytotoxicity and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro. Among them, 8 showed potent AChE inhibitory activity, with an IC50 value of 1.31 μM, and 5 showed significant cytotoxicity against PC-3 cells, with an IC50 value of 2.32 μM. [ABSTRACT FROM AUTHOR]
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- 2022
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21. Toxicity effects of mycotoxins and autophagy: a mechanistic view.
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Ariafar, Saba, Oftadeh Harsin, Akram, Fadaiie, Ahmad, Mahboobian, Mohammad Mehdi, and Mohammadi, Mojdeh
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CELL survival ,AUTOPHAGY ,CELL death ,MYCOTOXINS ,METABOLITES ,HOMEOSTASIS ,AFLATOXINS - Abstract
Mycotoxins are secondary metabolites of fungi that contaminate a wide range of foods and feeds. Autophagy is a highly conservative cell behavior to keep the intracellular homeostasis and is frequently active in disgusting conditions, such as starvation, hypoxia, and the presence of cytotoxic agents. However, the precise role of autophagy under various conditions may be opposite, from promoting cells survival to cells death, and the mechanism of this conditional-dependent role is still unclear. The greatest important question – whether autophagy has a defensive role or a damaging one – is not obviously recognized. In this review, we give an overview of the roles of autophagy in mycotoxin toxicity and cell death. Also, we explain how autophagy is the implication of this regulation to mycotoxin toxicity. [ABSTRACT FROM AUTHOR]
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- 2021
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22. New curtachalasin from the Xylaria sp. DO 1801.
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Wang, Jia, Sang, Yining, Tang, Siqi, and Zhang, Peng
- Subjects
XYLARIA ,CYTOCHALASINS ,ETHYL acetate ,X-ray spectra ,CELL lines - Abstract
One new cytochalasin, named curtachalasin Q (1), together with 8 known cytochalasins were isolated from the ethyl acetate extract of the Xylaria sp. DO1801. The structure of the new compound was elucidated on the basis of IR, UV, HR-ESI-MS, NMR spectra and X-ray diffraction. Compound 1 and 2 were not cytotoxic (IC
50 >50uM) against four tumour cell lines (SW-1990, ASPC-1, HepG2 and Hep3B). [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
23. Six Unprecedented Cytochalasin Derivatives from the Potato Endophytic Fungus Xylaria curta E10 and Their Cytotoxicity
- Author
-
Xian Zhang, Yinzhong Fan, Ke Ye, Xiaoyan Pan, Xujun Ma, Honglian Ai, Baobao Shi, and Jikai Liu
- Subjects
endophyte fungus ,Xylaria curta ,cytochalasins ,isolation and structure elucidation ,cytotoxicity ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Six previously undescribed cytochalasins, Curtachalasins X1–X6 (1–6), together with six known compounds (7–12) were isolated from the endophytic fungus Xylaria curta E10 harbored in the plant Solanum tuberosum. The structures were elucidated by the interpretation of HRESIMS, UV, and NMR data. The absolute configurations of Curtachalasins X1–X6 were determined by comparison of their experimental and calculated electronic circular dichroism (ECD) spectra. In bioassays, Curtachalasin X1 (1) and X5 (5) showed cytotoxic activity against the MCF-7 cell line with IC50 values of 2.03 μM and 0.85 μM, respectively.
- Published
- 2023
- Full Text
- View/download PDF
24. Cytochalasins from endophytic Diaporthe sp. GDG-118.
- Author
-
Huang, Xishan, Zhou, Dexiong, Liang, Yan, Liu, Xiaobo, Cao, Fei, Qin, Yuyue, Mo, Tuxiang, Xu, Zhaolong, Li, Jun, and Yang, Ruiyun
- Subjects
CYTOCHALASINS ,CHINESE medicine ,ENDOPHYTIC fungi ,ALTERNARIA ,SOPHORA - Abstract
The plant Sophora tonkinensis, possessed a range of active compounds, was traditionally used in the medicine of Chinese minorities. Endophytic fungi were isolated from this plant, of which the fungus Diaporthe sp. GDG-118 was fermented and extracted with methanol. The extract was screened by antifungal and antibacterial assays leading to the discovery of two new 21-acetoxycytochalasins (1–2) and five known cytochalasins (3–7). These two new compounds were elucidated by spectroscopic analyses, and further their absolute configurations were determined by the X-ray of compound 3 and comparing their experimental CD spectra. The antibacterial and antifungal effects of these compounds were evaluated. Compound 2 showed significant inhibitory activity against Bacillus anthraci and Escherichia coli with MIC value of 12.5 μg/mL, and 7 showed strong antifungal activity against Alternaria oleracea, Pestalotiopsis theae and Colletotrichum capsici with MIC values of 3.125, 1.56 and 1.56 μg/mL, respectively. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
25. Oral intake of rice overexpressing ubiquitin ligase inhibitory pentapeptide prevents atrophy in denervated skeletal muscle.
- Author
-
Nakao, Reiko, Shen, Weilin, Shimajiri, Yasuka, Kainou, Kumiko, Sato, Yuki, Ulla, Anayt, Ohnishi, Kohta, Ninomiya, Miyuki, Ohno, Ayako, Uchida, Takayuki, Tanaka, Mitsuru, Akama, Kazuhito, Matsui, Toshiro, and Nikawa, Takeshi
- Subjects
UBIQUITIN ligases ,INTRAMUSCULAR injections ,MUSCULAR atrophy ,CYTOCHALASINS ,MUSCLE mass - Abstract
We previously reported that intramuscular injections of ubiquitin ligase CBLB inhibitory pentapeptide (Cblin; Asp-Gly-pTyr-Met-Pro) restored lost muscle mass caused by sciatic denervation. Here, we detected Cblin on the basolateral side of Caco-2 cells after being placed on the apical side, and found that cytochalasin D, a tight junction opener, enhanced Cblin transport. Orally administered Cblin was found in rat plasma, indicating that intact Cblin was absorbed in vitro and in vivo. Furthermore, transgenic Cblin peptide-enriched rice (CbR) prevented the denervation-induced loss of muscle mass and the upregulation of muscle atrophy-related ubiquitin ligases in mice. These findings indicated that CbR could serve as an alternative treatment for muscle atrophy. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
26. Studies from Inha University Further Understanding of Cancer (Cytochalasin B-induced Membrane Vesicles of Nk Cells for Efficient Tumor Immunotherapy).
- Abstract
A study conducted at Inha University in Incheon, South Korea, has explored the use of cytochalasin B-induced membrane vesicles (CIMVs) derived from natural killer (NK) cells for tumor immunotherapy. These CIMVs were found to be more concentrated and contain more proteins with immunological activity against tumors compared to isolated natural extracellular vesicles (EVs) from NK cells. The study demonstrated that administering these CIMVs to tumor cells induced caspase-dependent apoptosis, leading to tumor cell cytotoxicity. This research contributes to the understanding of NK vesicles' role in cellular communication and immunity and highlights the therapeutic potential of engineered NK-EVs for specific action on tumor cells. [Extracted from the article]
- Published
- 2024
27. Researchers from Chinese Academy of Sciences Discuss Research in Prostate Cancer (Novel Metabolites from the Marine-Derived Fungus Peniophora sp. SCSIO41203 Show Promising In Vitro Antitumor Activity as Methuosis Inducers in PC-3 Cells).
- Abstract
A recent report discusses new research on prostate cancer conducted by researchers from the Chinese Academy of Sciences. The researchers isolated several compounds from the marine-derived fungus Peniophora sp. SCSIO41203, including two cytochalasin derivatives, three citrinin derivatives, and one tetramic acid derivative. These compounds were found to have promising anti-prostate cancer activity, with one compound showing significant anti-prostate cancer cell proliferation effects. The researchers also discovered that this compound induces methuosis, making it a potential anti-prostate methuosis inducer. Further details of the research can be found in the journal article "Novel Metabolites from the Marine-Derived Fungus Peniophora sp. SCSIO41203 Show Promising In Vitro Antitumor Activity as Methuosis Inducers in PC-3 Cells." [Extracted from the article]
- Published
- 2024
28. Research on Regenerative Medicine Reported by a Researcher at Kazan Federal University (Artificial Extracellular Vesicles Generated from T Cells Using Different Induction Techniques).
- Abstract
A researcher at Kazan Federal University in Russia has conducted research on regenerative medicine, specifically focusing on the use of artificial extracellular vesicles (EVs) as a cell-free therapy modality. The study evaluated two primary approaches for inducing artificial vesicles in T cells: cytochalasin B as a chemical inducer and ultrasonication as a physical inducer. The research found that both methods were capable of producing artificial vesicles, with cytochalasin B induction resulting in a higher yield compared to natural secretion, and ultrasonication leading to a three-fold increase in particle yield. The most effective approach for T-cell induction was found to be a combination of anti-CD3/CD28 antibody activation with ultrasonication, resulting in a seven-fold yield increase in particles with a high content of functionally important proteins. This research provides valuable insights into the potential use of artificial EVs in regenerative medicine. [Extracted from the article]
- Published
- 2024
29. Epigenetic Manipulation Induced Production of Immunosuppressive Chromones and Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48
- Author
-
Ting Feng, Chengwen Wei, Xiaolin Deng, Dandan Chen, Zhenchang Wen, and Jing Xu
- Subjects
mangrove endophytic fungus ,Phomopsis asparagi ,epigenetic manipulation ,chromones ,cytochalasins ,Biology (General) ,QH301-705.5 - Abstract
A mangrove endophytic fungus Phomopsis asparagi DHS-48 was found to be particularly productive with regard to the accumulation of substantial new compounds in our previous study. In order to explore its potential to produce more unobserved secondary metabolites, epigenetic manipulation was used on this fungus to activate cryptic or silent genes by using the histone deacetylase (HDAC) inhibitor sodium butyrate and the DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-Aza). Based on colony growth, dry biomass, HPLC, and 1H NMR analyses, the fungal chemical diversity profile was significantly changed compared with the control. Two new compounds, named phaseolorin J (1) and phomoparagin D (5), along with three known chromones (2–4) and six known cytochalasins (6–11), were isolated from the culture treated with sodium butyrate. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD and 13C NMR calculations. The immunosuppressive and cytotoxic activities of all isolated compounds were evaluated. Compounds 1 and 8 moderately inhibited the proliferation of ConA (concanavalin A)-induced T and LPS (lipopolysaccharide)-induced B murine spleen lymphocytes. Compound 5 exhibited significant in vitro cytotoxicity against the tested human cancer cell lines Hela and HepG2, which was comparative to the positive control adriamycin and fluorouracil. Our finding demonstrated that epigenetic manipulation should be an efficient strategy for the induction of new metabolites from mangrove endophytic fungi.
- Published
- 2022
- Full Text
- View/download PDF
30. Immunosuppressive Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48
- Author
-
Zhao Feng, Xuexia Zhang, Jingwan Wu, Chengwen Wei, Ting Feng, Dongdong Zhou, Zhenchang Wen, and Jing Xu
- Subjects
mangrove endophytic fungi ,Phomopsis sp. ,cytochalasins ,immunosuppressive activity ,CaN/NFAT signaling pathway ,Biology (General) ,QH301-705.5 - Abstract
Three new cytochalasins, phomoparagins A-C (1–3), along with five known analogs (4–8), were isolated from Phomopsis asparagi DHS-48, a mangrove-derived endophytic fungus. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD techniques. Notably, 1 possessed an unprecedented 5/6/5/8/5-fused pentacyclic skeleton. These compounds were tested for their inhibitory activity against concanavalin A (ConA)/lipopolysaccharide (LPS)-induced spleen lymphocyte proliferation and calcineurin (CN) enzyme. Several metabolites (2 and 4–6) exhibited fascinating inhibitory activities with a relatively low toxicity. Furthermore, 2 was demonstrated to inhibit ConA-stimulated activation of NFAT1 dephosphorylation and block NFAT1 translocation in vitro, subsequently inhibiting the transcription of interleukin-2 (IL-2). Our results provide evidence that 2 may, at least partially, suppress the activation of spleen lymphocytes via the CN/NFAT signaling pathway, highlighting that it could serve as an effective immunosuppressant that is noncytotoxic and natural.
- Published
- 2022
- Full Text
- View/download PDF
31. 3D printed microfluidic lab-on-a-chip device for fiber-based dual beam optical manipulation.
- Author
-
Wang, Haoran, Enders, Anton, Preuss, John-Alexander, Bahnemann, Janina, Heisterkamp, Alexander, and Torres-Mapa, Maria Leilani
- Subjects
- *
MICROFLUIDICS , *THREE-dimensional printing , *HYDRODYNAMICS , *CYTOCHALASINS , *OPTICAL fibers - Abstract
3D printing of microfluidic lab-on-a-chip devices enables rapid prototyping of robust and complex structures. In this work, we designed and fabricated a 3D printed lab-on-a-chip device for fiber-based dual beam optical manipulation. The final 3D printed chip offers three key features, such as (1) an optimized fiber channel design for precise alignment of optical fibers, (2) an optically clear window to visualize the trapping region, and (3) a sample channel which facilitates hydrodynamic focusing of samples. A square zig–zag structure incorporated in the sample channel increases the number of particles at the trapping site and focuses the cells and particles during experiments when operating the chip at low Reynolds number. To evaluate the performance of the device for optical manipulation, we implemented on-chip, fiber-based optical trapping of different-sized microscopic particles and performed trap stiffness measurements. In addition, optical stretching of MCF-7 cells was successfully accomplished for the purpose of studying the effects of a cytochalasin metabolite, pyrichalasin H, on cell elasticity. We observed distinct changes in the deformability of single cells treated with pyrichalasin H compared to untreated cells. These results demonstrate that 3D printed microfluidic lab-on-a-chip devices offer a cost-effective and customizable platform for applications in optical manipulation. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
32. Two new cytochalasins from Chaetomium sp. Strain.
- Author
-
Zhao, Miao, Xian, Xiao-Ya, Liang, Lin, Gao, Jin-Tao, Wang, Li-Sheng, Zhou, Xian-Li, and Liang, Cheng-Qin
- Subjects
- *
CYTOCHALASINS , *CHAETOMIUM , *MOLECULAR docking , *ALPHA-glucosidases , *METABOLITES - Abstract
[Display omitted] Two new compounds armochaetoglosin A1 (1) and armochaetoglosin A2 (2), together with three known compounds (3 – 5), were isolated from Chaetomium sp. Strain. Their structures were elucidated based on spectroscopic methods, including extensive NMR and MS spectra. Compound 5 showed potential inhibitory activity on α -glucosidase with the IC 50 value of 38.81 ± 8.08 µM. Molecular docking studies confirmed our result on compound 5 α -glucosidase inhibitory properties. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
33. Exploring the elasticity and adhesion behavior of cardiac fibroblasts by atomic force microscopy indentation
- Author
-
Codan, B, Del Favero, G, Martinelli, V, Long, CS, Mestroni, L, and Sbaizero, O
- Subjects
Engineering ,Materials Engineering ,Biomedical Engineering ,Animals ,Cell Adhesion ,Cells ,Cultured ,Cytochalasins ,Cytoskeleton ,Elasticity ,Fibroblasts ,Mice ,Microscopy ,Atomic Force ,Myocytes ,Cardiac ,Cell ,Adhesion ,Cardiac fibroblast ,AFM ,Biomedical engineering ,Materials engineering - Abstract
AFM was used to collect the whole force-deformation cell curves. They provide both the elasticity and adhesion behavior of mouse primary cardiac fibroblasts. To confirm the hypothesis that a link exists between the membrane receptors and the cytoskeletal filaments causing therefore changing in both elasticity and adhesion behavior, actin-destabilizing Cytochalsin D was administrated to the fibroblasts. From immunofluorescence observation and AFM loading/unloading curves, cytoskeletal reorganization as well as a change in the elasticity and adhesion was indeed observed. Elasticity of control fibroblasts is three times higher than that for fibroblasts treated with 0.5 μM Cytochalasin. Moreover, AFM loading-unloading curves clearly show the different mechanical behavior of the two different cells analyzed: (i) for control cells the AFM cantilever rises during the dwell time while cells with Cytochalasin fail to show such an active resistance; (ii) the maximum force to deform control cells is quite higher and as far as adhesion is concern (iii) the maximum separation force, detachment area and the detachment process time are much larger for control compared to the Cytochalasin treated cells. Therefore, alterations in the cytoskeleton suggest that a link must exist between the membrane receptors and the cytoskeletal filaments beneath the cellular surface and inhibition of actin polymerization has effects on the whole cell mechanical behavior as well as adhesion.
- Published
- 2014
34. A carbonate-forming Baeyer-Villiger monooxygenase
- Author
-
Hu, Youcai, Dietrich, David, Xu, Wei, Patel, Ashay, Thuss, Justin AJ, Wang, Jingjing, Yin, Wen-Bing, Qiao, Kangjian, Houk, KN, Vederas, John C, and Tang, Yi
- Subjects
Biological Sciences ,Genetics ,Amino Acid Sequence ,Aspergillus ,Carbonates ,Catalysis ,Cytochalasins ,Fungal Proteins ,Gene Expression Regulation ,Fungal ,Gene Knockout Techniques ,Genetic Complementation Test ,Ketones ,Mixed Function Oxygenases ,Oxidation-Reduction ,Medicinal and Biomolecular Chemistry ,Biochemistry and Cell Biology ,Biochemistry & Molecular Biology ,Biochemistry and cell biology ,Medicinal and biomolecular chemistry - Abstract
Despite the remarkable versatility displayed by flavin-dependent monooxygenases (FMOs) in natural product biosynthesis, one notably missing activity is the oxidative generation of carbonate functional groups. We describe a multifunctional Baeyer-Villiger monooxygenase, CcsB, which catalyzes the formation of an in-line carbonate in the macrocyclic portion of cytochalasin E. This study expands the repertoire of activities of FMOs and provides a possible synthetic strategy for transformation of ketones into carbonates.
- Published
- 2014
35. An NMR Analysis of 10-Indol Cytochalasin Chaetoglobosin F
- Author
-
YIN Tian-peng, WANG Ze, CHEN Yang, SHAO Ya-ting, DENG Liang, and LI Wei
- Subjects
cytochalasins ,chaetoglobosin F ,indol ,nuclear magnetic resonance (NMR) ,structural elucidation ,Electricity and magnetism ,QC501-766 - Abstract
Cytochalasins are a group of natural products from fungus, and have been attracting lots of research interests in the field of microbiology. Cytochalasins possess complex and diverse structures, making nuclear magnetic resonance (NMR) based structure elucidation difficult. Chaetoglobosin F is a 10-indol cytochalasin isolated from endophytic Chaetomium globosum growing in the seeds of Panax notoginseng. This paper reported the NMR data chaetoglobosin F, along with the summarization of NMR features of 10-indol cytochalasins, providing a good reference for the further research on cytochalasins.
- Published
- 2019
- Full Text
- View/download PDF
36. Cytochalasins from Xylaria sp. CFL5, an Endophytic Fungus of Cephalotaxus fortunei.
- Author
-
Ma, Kai-Liang, Dong, Shi-Hui, Li, Hang-Ying, Wei, Wen-Jun, Tu, Yong-Qiang, and Gao, Kun
- Subjects
CYTOCHALASINS ,XYLARIA ,OPTICAL rotation ,CIRCULAR dichroism ,ENDOPHYTIC fungi ,CHEMICAL structure - Abstract
Three previously undescribed cytochalasins, named xylariasins A‒C (1‒3), together with six known ones (4‒9) were isolated from Xylaria sp. CFL5, an endophytic fungus of Cephalotaxus fortunei. The chemical structures of all new compounds were elucidated on the basis of extensive spectroscopic data analyses and electronic circular dichroism calculation, as well as optical rotation calculation. Biological activities of compounds 1, 4‒9 were evaluated, including cytotoxic, LAG3/MHC II binding inhibition and LAG3/FGL1 binding inhibition activities. Compounds 6 and 9 possessed cytotoxicity against AGS cells at 5 μM, with inhibition rates of 94% and 64%, respectively. In addition, all tested isolates, except compound 6, exhibited obvious inhibitory activity against the interaction of both LAG3/MHC II and LAG3/FGL1. Compounds 1, 5, 7, and 8 inhibited LAG3/MHC II with IC
50 values ranging from 2.37 to 4.74 μM. Meanwhile, the IC50 values of compounds 1, 7, and 8 against LAG3/FGL1 were 11.78, 4.39, and 7.45 μM, respectively. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
37. Novel 6/7/6 ring system diterpenoids and cytochalasins from the fungus Eutypella scoparia GZU-4-19Y and their anti-inflammatory activity.
- Author
-
He J, Zou Q, Deng H, He S, Yan D, Pan K, Zhou Y, Zhao Z, Cui H, and Liu Y
- Subjects
- Molecular Structure, Anti-Inflammatory Agents pharmacology, Abietanes, Cytochalasins, Ascomycota chemistry, Diterpenes pharmacology, Indoles, Lactones
- Abstract
Two new compounds eutyditerpenoid A (1) and seco-phenochalasin B (5), together with seven known compounds diaporthein A (2), aspergillon A (3), phenochalasin B (4), cytochalasins Z
24 and Z25 (6 and 7), scoparasins A and B (8 and 9) were isolated from marine-derived Eutypella scoparia GZU-4-19Y. Among them, eutyditerpenoid A (1) with a rare 6/7/6 ring system possesing an anhydride moiety was the first example in the pimarane-type diterpenoids. Their structures were determined based on spectroscopic methods and the electronic circular dichroism (ECD) calculations. In the bioassays, all of the isolates were evaluated for their inhibitory activity against NO production induced by lipopolysaccharide in RAW 264.7 cells. Compounds 3 and 7 showed potent NO inhibition activity with IC50 values of 2.1 and 17.1 μM respectively, and the former also significantly suppressed the protein expression of iNOS and COX-2 at the concentration of 2.5 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)- Published
- 2024
- Full Text
- View/download PDF
38. Identification of the Antifungal Metabolite Chaetoglobosin P From Discosia rubi Using a Cryptococcus neoformans Inhibition Assay: Insights Into Mode of Action and Biosynthesis
- Author
-
Bruno Perlatti, Connie B. Nichols, Nan Lan, Philipp Wiemann, Colin J. B. Harvey, J. Andrew Alspaugh, and Gerald F. Bills
- Subjects
actin ,β-methyltryptophan ,cytochalasins ,Stenocarpella macrospora ,twinfilin-1 ,Xylariales ,Microbiology ,QR1-502 - Abstract
Cryptococcus neoformans is an important human pathogen with limited options for treatments. We have interrogated extracts from fungal fermentations to find Cryptococcus-inhibiting natural products using assays for growth inhibition, differential thermosensitivity, and synergy with existing antifungal drugs. Extracts from fermentations of strains of Discosia rubi from eastern Texas showed anticryptococcal bioactivity with preferential activity in agar zone of inhibition assays against C. neoformans at 37°C versus 25°C. Assay-guided fractionation led to the purification and identification of chaetoglobosin P as the active component of these extracts. Genome sequencing of these strains revealed a biosynthetic gene cluster consistent with chaetoglobosin biosynthesis and β-methylation of the tryptophan residue. Proximity of genes of the actin-binding protein twinfilin-1 to the chaetoglobosin P and K gene clusters suggested a possible self-resistance mechanism involving twinfilin-1 which is consistent with the predicted mechanism of action involving interference with the polymerization of the capping process of filamentous actin. A C. neoformans mutant lacking twinfilin-1 was hypersensitive to chaetoglobosin P. Chaetoglobosins also potentiated the effects of amphotericin B and caspofungin on C. neoformans.
- Published
- 2020
- Full Text
- View/download PDF
39. Study Findings from University of Chemistry and Technology Prague Provide New Insights into Medicinal Chemistry (Synthesis and Migrastatic Activity of Cytochalasin Analogues Lacking a Macrocyclic Moiety).
- Published
- 2024
40. Diversely Functionalised Cytochalasins through Mutasynthesis and Semi‐Synthesis.
- Author
-
Wang, Chongqing, Lambert, Christopher, Hauser, Maurice, Deuschmann, Adrian, Zeilinger, Carsten, Rottner, Klemens, Stradal, Theresia E. B., Stadler, Marc, Skellam, Elizabeth J., and Cox, Russell J.
- Subjects
- *
CYTOCHALASINS , *MICROFILAMENT proteins , *PYRICULARIA grisea , *RING formation (Chemistry) , *BIOLOGICAL assay , *IN vivo studies - Abstract
Mutasynthesis of pyrichalasin H from Magnaporthe grisea NI980 yielded a series of unprecedented 4′‐substituted cytochalasin analogues in titres as high as the wild‐type system (≈60 mg L−1). Halogenated, O‐alkyl, O‐allyl and O‐propargyl examples were formed, as well as a 4′‐azido analogue. 4′‐O‐Propargyl and 4′‐azido analogues reacted smoothly in Huisgen cycloaddition reactions, whereas p‐Br and p‐I compounds reacted in Pd‐catalysed cross‐coupling reactions. A series of examples of biotin‐linked, dye‐linked and dimeric cytochalasins was rapidly created. In vitro and in vivo bioassays of these compounds showed that the 4′‐halogenated and azido derivatives retained their cytotoxicity and antifungal activities; but a unique 4′‐amino analogue was inactive. Attachment of larger substituents attenuated the bioactivities. In vivo actin‐binding studies with adherent mammalian cells showed that actin remains the likely intracellular target. Dye‐linked compounds revealed visualisation of intracellular actin structures even in the absence of phalloidin, thus constituting a potential new class of actin‐visualisation tools with filament‐barbed end‐binding specificity. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
41. Identification of the Antifungal Metabolite Chaetoglobosin P From Discosia rubi Using a Cryptococcus neoformans Inhibition Assay: Insights Into Mode of Action and Biosynthesis.
- Author
-
Perlatti, Bruno, Nichols, Connie B., Lan, Nan, Wiemann, Philipp, Harvey, Colin J. B., Alspaugh, J. Andrew, and Bills, Gerald F.
- Subjects
CRYPTOCOCCUS neoformans ,MICROFILAMENT proteins ,BIOSYNTHESIS ,GENE clusters ,AMPHOTERICIN B ,ANTIFUNGAL agents - Abstract
Cryptococcus neoformans is an important human pathogen with limited options for treatments. We have interrogated extracts from fungal fermentations to find Cryptococcus -inhibiting natural products using assays for growth inhibition, differential thermosensitivity, and synergy with existing antifungal drugs. Extracts from fermentations of strains of Discosia rubi from eastern Texas showed anticryptococcal bioactivity with preferential activity in agar zone of inhibition assays against C. neoformans at 37°C versus 25°C. Assay-guided fractionation led to the purification and identification of chaetoglobosin P as the active component of these extracts. Genome sequencing of these strains revealed a biosynthetic gene cluster consistent with chaetoglobosin biosynthesis and β-methylation of the tryptophan residue. Proximity of genes of the actin-binding protein twinfilin-1 to the chaetoglobosin P and K gene clusters suggested a possible self-resistance mechanism involving twinfilin-1 which is consistent with the predicted mechanism of action involving interference with the polymerization of the capping process of filamentous actin. A C. neoformans mutant lacking twinfilin-1 was hypersensitive to chaetoglobosin P. Chaetoglobosins also potentiated the effects of amphotericin B and caspofungin on C. neoformans. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
42. Immunosuppressive properties of cytochalasin B-induced membrane vesicles of mesenchymal stem cells: comparing with extracellular vesicles derived from mesenchymal stem cells.
- Author
-
Gomzikova, M. O., Aimaletdinov, A. M., Bondar, O. V., Starostina, I. G., Gorshkova, N. V., Neustroeva, O. A., Kletukhina, S. K., Kurbangaleeva, S. V., Vorobev, V. V., Garanina, E. E., Persson, J. L., Jeyapalan, J., Mongan, N. P., Khaiboullina, S. F., and Rizvanov, A. A.
- Subjects
- *
IMMUNOSUPPRESSIVE agents , *CYTOCHALASINS , *VESICLES (Cytology) , *MESENCHYMAL stem cells , *IMMUNOPHENOTYPING - Abstract
Extracellular vesicles derived from mesenchymal stem cells (MSCs) represent a novel approach for regenerative and immunosuppressive therapy. Recently, cytochalasin B-induced microvesicles (CIMVs) were shown to be effective drug delivery mediators. However, little is known about their immunological properties. We propose that the immunophenotype and molecular composition of these vesicles could contribute to the therapeutic efficacy of CIMVs. To address this issue, CIMVs were generated from murine MSC (CIMVs-MSCs) and their cytokine content and surface marker expression determined. For the first time, we show that CIMVs-MSCs retain parental MSCs phenotype (Sca-1+, CD49e+, CD44+, CD45−). Also, CIMVs-MSCs contained a cytokine repertoire reflective of the parental MSCs, including IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12(p40), IL-13, IL-17, CCL2, CCL3, CCL4, CCL5, CCL11, G-CSF, GM-CSF and TNF-α. Next, we evaluated the immune-modulating properties of CIMVs-MSCs in vivo using standard preclinical tests. MSCs and CIMVs-MSCs reduced serum levels of anti-sheep red blood cell antibody and have limited effects on neutrophil and peritoneal macrophage activity. We compared the immunomodulatory effect of MSCs, CIMVs and EVs. We observed no immunosuppression in mice pretreated with natural EVs, whereas MSCs and CIMVs-MSCs suppressed antibody production in vivo. Additionally, we have investigated the biodistribution of CIMVs-MSCs in vivo and demonstrated that CIMVs-MSCs localized in liver, lung, brain, heart, spleen and kidneys 48 h after intravenous injection and can be detected 14 days after subcutaneous and intramuscular injection. Collectively our data demonstrates immunomodulatory efficacy of CIMVs and supports their further preclinical testing as an effective therapeutic delivery modality. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
43. Spatiotemporal force and motion in collective cell migration.
- Author
-
Saraswathibhatla, Aashrith, Galles, Emmett E., and Notbohm, Jacob
- Subjects
CELL migration ,METASTASIS ,WOUND healing ,ACTOMYOSIN ,CYTOCHALASINS - Abstract
Cells move in collective groups in biological processes such as wound healing, morphogenesis, and cancer metastasis. How active cell forces produce the motion in collective cell migration is still unclear. Many theoretical models have been introduced to elucidate the relationship between the cell's active forces and different observations about the collective motion such as collective swirls, oscillations, and rearrangements. Though many models share the common feature of balancing forces in the cell layer, the specific relationships between force and motion vary among the different models, which can lead to different conclusions. Simultaneous experimental measurements of force and motion can aid in testing assumptions and predictions of the theoretical models. Here, we provide time-lapse images of cells in 1 mm circular islands, which are used to compute cell velocities, cell-substrate tractions, and monolayer stresses. Additional data are included from experiments that perturbed cell number density and actomyosin contractility. We expect this data set to be useful to researchers interested in force and motion in collective cell migration. Measurement(s) force • Motion • MDCK cell • cell migration Technology Type(s) in vitro microscopy with digital image analysis • time-lapse microscopy Factor Type(s) cell number density • cytochalasin D • CN03 Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12378218 [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
44. Three-dimensional real time imaging of amyloid β aggregation on living cells.
- Author
-
Kuragano, Masahiro, Yamashita, Ryota, Chikai, Yusaku, Kitamura, Ryota, and Tokuraku, Kiyotaka
- Subjects
- *
AMYLOID , *ALZHEIMER'S disease , *LANGUAGE ability , *CELL death , *CYTOCHALASINS - Abstract
Alzheimer's disease (AD) is a progressive disorder of the brain that gradually decreases thinking, memory, and language abilities. The aggregation process of amyloid β (Aβ) is a key step in the expression of its neurocytotoxicity and development of AD because Aβ aggregation and accumulation around neuronal cells induces cell death. However, the molecular mechanism underlying the neurocytotoxicity and cell death by Aβ aggregation has not been clearly elucidated. In this study, we successfully visualized real-time process of Aβ42 aggregation around living cells by applying our established QD imaging method. 3D observations using confocal laser microscopy revealed that Aβ42 preferentially started to aggregate at the region where membrane protrusions frequently formed. Furthermore, we found that inhibition of actin polymerization using cytochalasin D reduced aggregation of Aβ42 on the cell surface. These results indicate that actin polymerization-dependent cell motility is responsible for the promotion of Aβ42 aggregation at the cell periphery. 3D observation also revealed that the aggregates around the cell remained in that location even if cell death occurred, implying that amyloid plaques found in the AD brain grew from the debris of dead cells that accumulated Aβ42 aggregates. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
45. Binding of phenochalasin A, an inhibitor of lipid droplet formation in mouse macrophages, on G-actin
- Author
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Keisuke, Kobayashi, Daisuke, Matsuda, Hiroshi, Tomoda, and Taichi, Ohshiro
- Subjects
Indoles ,CHO Cells ,Lipid Droplets ,General Medicine ,Cytochalasins ,Actins ,Iodine Radioisotopes ,Lactones ,Mice ,Cricetulus ,Phenols ,Cricetinae ,Macrophages, Peritoneal ,Animals ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics - Abstract
Phenochalasin A, a unique phenol-containing cytochalasin produced by the marine-derived fungus Phomopsis sp. FT-0211, was originally discovered in a cell morphological assay of observing the inhibition of lipid droplet formation in mouse peritoneal macrophages. To investigate the mode of action and binding proteins, phenochalasin A was radio-labeled by
- Published
- 2022
46. Pentacyclic Cytochalasins and Their Derivatives from the Endophytic Fungus Phomopsis sp. xz-18
- Author
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Guichon Huang, Weiwen Lin, Hanpeng Li, Qian Tang, Zhiyu Hu, Huiying Huang, Xianming Deng, and Qingyan Xu
- Subjects
cytochalasins ,pentacyclic system ,octant rule ,antibacterial activity ,Organic chemistry ,QD241-441 - Abstract
Eight new cytochalasins 1–8 and ten known analogs 9–18 were isolated from the endophytic fungus Phomopsis sp. xz-18. The planar structures of the cytochalasins were determined by HR-ESI-MS and NMR analysis. Compounds 1, 2, 9 and 10 were 5/6/6/7/5-fused pentacyclic cytochalasins; compounds 3 and 4 had conjugated diene structures in the macrocycle; and compound 6 had a β,γ-unsaturated ketone. The absolute configuration of 6 was confirmed for the first time by the octant rule. The acid-free purification process proved that the pentacyclic system was a natural biosynthetic product and not an acid-mediated intramolecular cyclized artifact. The new compounds did not exhibit activities against human cancer cell lines in cytotoxicity bioassays or antipathogenic fungal activity, but compounds 1, 3 and 4 showed moderate antibacterial activity in disk diffusion assays.
- Published
- 2021
- Full Text
- View/download PDF
47. Zopfiellasins A–D, Two Pairs of Epimeric Cytochalasins from Kiwi-Associated Fungus Zopfiella sp. and Their Antibacterial Assessment
- Author
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Jie-Yu Zhang, Juan He, Zheng-Hui Li, Tao Feng, and Ji-Kai Liu
- Subjects
Zopfiella sp. ,cytochalasins ,Pseudomonas syringae pv. actinidiae ,antibacterial ,Organic chemistry ,QD241-441 - Abstract
In our continuous search for antibacterial agents against Pseudomonas syringae pv. actinidiae (Psa) from kiwi-associated fungi, two pairs of epimeric cytochalasins, zopfiellasins A–D (1–4), were characterized from the fungus Zopfiella sp. The structures were established on the basis of spectroscopic data analysis, while the absolute configurations were determined by single-crystal X-ray diffraction. Compounds 1 and 3 exhibited antibacterial activity against Psa with MIC values of 25 and 50 μg/mL, respectively. This is the first report of anti-Psa activity of cytochalasin derivatives.
- Published
- 2021
- Full Text
- View/download PDF
48. PITSTOP-2 AND DYNASORE EXPOSURE REDUCED TREHALOSE ENTRY INTO HUMAN DERMAL FIBROBLAST.
- Author
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Kusuma, I., Hadi, R. S., Kiranadi, B., and Boediono, A.
- Subjects
TREHALOSE ,FIBROBLASTS ,ENDOCYTOSIS ,CRYOPRESERVATION of cells ,CYTOCHALASINS - Abstract
Trehalose is a natural cell preservation agent with the inability to cross the mammalian cellular membrane which limits its preservative action to the extracellular compartment. In order to address this, endocytosis was identified as the cellular mechanism that allowed trehalose entry. The cellular machinery behind endocytosis is complex and required inhibitors to reveal a specific mechanism that facilitates the entry of trehalose. This study, therefore, used human dermal fibroblast cultured and incubated in different trehalose extracellular concentrations and incubation times. The trehalase-based assay was used to calculate the intracellular trehalose and FITC was used to indicate the trehalose entry in a PKH26 membrane-stained fibroblast. Pitstop-2, dynasore and cytochalasin-D were used to inhibit trehalose entry. Cryopreservation used the slow-freezing method using the trehalose as cryomedium. Intracellular trehalose was accumulated in a time and concentration-dependent manner. Pitstop-2, dynasore, and the combination of both inhibitors reduced as much as 60% of the trehalose entry. Cytochalasin-D also reduced the trehalose entry in a dose-dependent manner. Additional pre-treatment incubation time and extracellular trehalose in cryomedium provided increased protection of the cryopreserved fibroblast in the trehalose. The presence of trehalose on both sides of the membrane also improved cellular adhesion. In conclusion, pitstop-2 and dynasore reduced the trehalose entry, indicating a clathrin-mediated mechanism. However, clathrin-independent, dynamin-independent, and actin engagement were also involved in facilitating trehalose entry. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
49. New cytotoxic natural products from the mangrove biome: covering the period 2007–2015.
- Author
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Pejin, Boris and Glumac, Miodrag
- Subjects
MANGROVE plants ,ORGANIC compounds ,CANCER ,MARINE fungi ,CYTOCHALASINS - Abstract
Nowadays, the mangrove biome is considered to be a profound resource of natural products usually possessing cytotoxicity of a broader range. Covering the period 2007–2015, a total of 21 new naturally occurring compounds has stood out. For example, xylogranin B and swietephragmin C were found to exhibit very potent cytotoxic activity against the colon HCT-116 cells reaching IC
50 values of 0.05 and 0.06 μM, respectively. Bearing in mind the efficacy of the majority compounds in the preliminary in vitro screens, these studies should be expanded to both ex vivo and in vivo screens including the evaluation of the relevant toxicological profiles. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
50. Evaluation of Tumor Regulatory Genes and Apoptotic Pathways in The Cytotoxic Effect of Cytochalasin H on Malignant Human Glioma Cell Line (U87MG).
- Author
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Heidarzadeh, Samaneh, Motalleb, Gholamreza, and Zorriehzahra, Mohammad Jalil
- Subjects
- *
APOPTOSIS , *CYTOCHALASINS , *CELL lines - Abstract
Objective: The aim of current study was to provide a proof-of-concept on the mechanism of PLAU and PCDH10 gene expressions and caspases-3, -8, and -9 activities in the apoptotic pathway after treatment of malignant human glioma cell line (U87MG) with cytochalasin H. Materials and Methods: In the present experimental study, we have examined cytochalasin H cytotoxic activities as a new therapeutic agent on U87MG cells in vitro for the first time. The cells were cultured and treated with 10-5-10-9 M of cytochalasin H for 24, 48 and 72 hours. The assessment of cell viability was carried out by (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazoliumbromide (MTT) assay at 578 nm. The data are the average of three independent tests. mRNA expression changes of PLAU and PCDH10 were then evaluated by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). The fluorometric of caspases-3, -8, and -9 activities were carried out. The morphology changes in the U87MG cells were observed by fluorescence microscope. Results: MTT assay showed that cytochalasin H (10-5 M) inhibited the U87MG cancer cells proliferation after 48 hours. Analysis of qRT-PCR showed that the PLAU expression was significantly decreased in comparison with the control (P<0.05). The expression of PCDH10 also showed a significant increase when compared to the control (P<0.001). Fluorescence microscope indicated morphological changes due to apoptosis in U87MG cancer cells, after treatment with cytochalasin H (10-5 M, 48 hours). The fluorometric evaluation of caspase-3, -8, and -9 activities showed no significant difference between the caspases and the control group. Conclusion: This study shows the effect of caspase-independent pathways of the programmed cell death on the U87MG cancer cell line under cytochalasin H treatment. Further studies are needed to explore the exact mechanism. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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