Search

Two new iridoid glycosides, piasezkiiosides A (1) and B (2), were isolated from aqueous extract of the whole plant of Rehmannia piasezkii. Their structures were established from the spectroscopic data, chemical transformation, and X-ray diffraction analysis. Compound 1 exhibited weak hepatoprotective activity against APAP-induced HepG2 cell damage. [ABSTRACT FROM AUTHOR]

We established myocardial injury models in vivo and in vitro to investigate the cardioprotective effect of gomisin D obtained from Schisandra chinensis. Gomisin D significantly inhibited isoproterenol-induced apoptosis and hypertrophy in H9C2 cells. Gomisin D decreased serum BNP, ANP, CK-MB, cTn-T levels and histopathological alterations, and inhibited myocardial hypertrophy in mice. In mechanisms research, gomisin D reversed ISO-induced accumulation of intracellular ROS and Ca2+. Gomisin D further improved mitochondrial energy metabolism disorders by regulating the TCA cycle. These results demonstrated that gomisin D had a significant effect on isoproterenol-induced myocardial injury by inhibiting oxidative stress, calcium overload and improving mitochondrial energy metabolism. [ABSTRACT FROM AUTHOR]

Four new iridoid glycosides (1–4), rehmaglutosides L–O, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known mellittoside (5) and ajugol (6) were also obtained in the current investigation, and the structure of mellittoside was unequivocally defined using X-ray diffraction data. Compounds 1–6 were tested for their cytotoxicity against five human tumor cell lines and proliferation effects on Lactobacillus Reuteri. [ABSTRACT FROM AUTHOR]

Seven new pentasaccharides (1–7), rehmaglupentasaccharides A-G, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known verbascose (8) and stachyose (9) were also obtained in the current investigation, and the structure of stachyose was unequivocally defined using X-ray diffraction data. Compounds 1–9 were tested for their cytotoxicity against five human tumor cell lines, influence on dopamine receptor activation, and proliferation effects against Lactobacillus reuteri. [ABSTRACT FROM AUTHOR]

Hair follicle (HF) undergo periodic growth and development in mammals, which regulated by dermal papilla cells (DPCs) are reported to play an important role in HF morphogenesis and development. However, primary DPCs have low proliferative activity, age quickly, and fresh cell isolation is both time-consuming and laborious. In this study, we introduced the SV40 large T antigen (SV40T) into dissociated early passage rabbit vibrissae DPCs with lentiviral vectors and established seven immortalized DPC lines (R-1, R-2, R-3, R-4, R-5, R-6 and R-7). These cell lines displayed early passage morphology and high alkaline phosphatase activity. RT-PCR and immunofluorescence staining showed that all the immortalized cell lines expressed the DPC markers (α-SMA, IGF1, ALPL, FGF2, BMP2 and TGFβ2), but α-SMA was only expressed well in R-3, R-4, and R-7. Furthermore, it was found that R-7 was the only line to survive beyond 50 passages. Compared to melanoma cells, R-7 did not undergo malignant transformation. Karyotyping and cell growth viability analysis illustrated that the R-7 cell line preserved the basic characteristics of primary DPCs. The R-7 DPCs established have potential application for future hair research. The study provides the theoretical basis in the cell research of HF growth and development. [ABSTRACT FROM AUTHOR]

Breast cancer is considered the most prevalent malignancy due to its high incidence rate, recurrence, and metastasis in women that makes it one of the deadliest cancers. The current study aimed to predict the genes associated with the recurrence and metastasis of breast cancer and to validate their effect on MDA-MB-231 cells. Through the bioinformatics analysis, the transcription factor 7 cofactor (MLLT11) as the target gene was obtained. MLLT11-specific siRNA was synthesized and transfected into MDA-MB-231 cells. The results demonstrated that the siRNA significantly reduced the MLLT11 mRNA levels. Moreover, cell migration and invasion, as well as the protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, matrix metalloproteinase (MMP) 2, and MMP9, were significantly lower in the groups treated with siRNA while the apoptosis was augmented. Collectively, MLLT11 siRNA elicited ameliorative properties on breast cancer cells, possibly via the inhibition of the PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

The phytochemical investigation on the fruits of Morinda citrifolia led to the isolation and characterization of a new anthraquinone, moricitrifone (1), along with seven known anthraquinones (2–8). The chemical structure of 1 was elucidated by extensive spectral analyses. The known compounds (2–8) were identified by comparing their spectral data with those reported in the literature. The antiproliferative activities of all isolated anthraquinones (1–8) against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 were evaluated in vitro. Compounds 1–8 exhibited remarkable antiproliferative activities with IC50 values ranging from 0.26 ± 0.05 to 16.58 ± 0.18 μM, which were comparable to those of doxorubicin. [ABSTRACT FROM AUTHOR]

Two new phenylpropanoids, 4-O-(1''-O-cis-caffeoyl)-β-glucopyran osyl-1-allyl-3-methoxy-benzene (1), 4'-O-(1''-O-cis-caffeoyl)-β-glucopyranosyl-hydroxymegastigm-4-en-3-one (2), together with nine known compounds were obtained from the leaves of Solanum capsicoides. Their structures were elucidated based on spectroscopic methods, and comparing spectral data with those in literature. Meanwhile, their anti-inflammatory activities were evaluated on (LPS)-induced RAW 246.7 cells, and 1, 9, and 10 showed better inhibitory effects with IC50 values of 17.19 ± 1.12, 18.15 ± 0.47, and 19.8 ± 0.95 μM, respectively. [ABSTRACT FROM AUTHOR]

A new aromatic glycoside (1) and twelve (2–13) known aromatic glycosides were isolated from the n-butyl alcohol of the 70% EtOH extract of the aerial part of Bupleurum chinense. Among them, compounds 4–7, 9, 11–13 were isolated from Umbelliferae plants for the first time. Their structures were elucidated by NMR and MS spectroscopy, and the absolute configuration of compound 1 was elucidated by single-crystal X-ray diffraction. Compounds 6 and 10 showed moderate cytotoxic activities on MGC-803 cell lines with IC50 values of 8.63 ± 0.08 and 13.65 ± 1.73 μM, respectively. [ABSTRACT FROM AUTHOR]

Four new ionones and ionone glycosides (1–4) were isolated from the whole plant of Rehmannia piasezkii Maxim. Their planar structures as well as absolute configuration were confirmed via spectroscopic analysis, ECD calculation, and X-ray crystallography. Compounds 1–4 were tested for their cytotoxicity against five human tumor cell lines and ability to inhibit LPS-activated NO production in the BV2 cell line. [ABSTRACT FROM AUTHOR]

Four new secoiridoids, syrretoside A (1), syrretoside B (2), 5β, 8β-syrretaglucone C(3), 5β, 8α-syrretaglucone C (4), together with eight known secoiridoids (5–12), were isolated from the stem barks of Syringa reticulata (Bl.) Hara. The structures of isolated compounds were established based on the physical and chemical means, NMR spectroscopy, high-resolution mass spectrometry (HR-ESI-MS), and circular dichroism spectrum (CD), as well as in comparison with the literature. The cytotoxicity of isolated compounds was investigated using CCK8 assay, which showed that these compounds had different degrees of inhibitory effect on two human tumor (MGC803, LN229) cell lines. [ABSTRACT FROM AUTHOR]

A total of 14 previously undescribed steroidal saponins named capsicsaponins A–N were isolated from the leaves of Solanum capsicoides , encompassing various types, including cholesterol derivatives and pseudospirostanol saponins. The structures of all compounds were determined through comprehensive analysis of spectroscopic data (1D NMR and 2D NMR), along with physicochemical analysis methods (acid hydrolysis, OR, and UV). Moreover, in the H 2 O 2 -induced pheochromocytoma cell line model, compounds 1 – 14 were screened for their neuroprotective effects on cells. The bioassay results demonstrated compounds 8 – 14 were able to revive cell viability compared to the positive control edaravone. The damage neuroprotection of the most active compound was further explored. [Display omitted] • 14 unreported steroidal saponins were isolated from Solanum capsicoides leaves. • The biological activity of 1 – 14 was screened in H 2 O 2 -induced PC-12 cells model. • Compounds 8 – 14 exhibited some degree of neuroprotective bioactivities. [ABSTRACT FROM AUTHOR]

Four new polyacetylene substances, sadivaethynes A–D, were isolated from the ethanol extract of the roots of Saposhnikovia divaricata (Turcz.) Schischk using repeated column chromatography. Structural elucidation of compounds 1–4 was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. All compounds were evaluated for cytotoxicity against two human cancer cell lines (MGC-803, Ishikawa) in vitro. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A novel schinortriterpenoid (SNT), schinensilactone A (1), characterized by a unique 7,8‐seco‐1,8‐cyclo‐schisanartane scaffold, was isolated from the leaves of Schisandra chinensis (Turcz.) Baill, together with a new SNT (schinensilactone B, 2) and two known (3, 4). Their structures were elucidated using spectroscopy and X‐ray diffraction. Furthermore, a hypothetical biosynthetic pathway for 1 was postulated due to its novel carbon skeleton. In addition, 1 exhibited significant anti‐proliferative activity against Caco‐2 cells originating from five different tumor cell lines, and its preliminary mechanism of action was investigated with respect to the expression of apoptosis‐related proteins, including P53, Caspase 3, Bax, PUMA, and Bcl2. These biological activities would further our understanding of the food function of Schisandra chinensis leaves. [ABSTRACT FROM AUTHOR]

Five new sesquiterpenoids, dictamtrinorguaianols E and F (1–2), and dictameudesmnosides F, G, and H (3–5), along with seven known sesquiterpenoids (6–12) were isolated from Dictamnus dasycarpus Turcz. The structures of all new compounds were characterized by spectroscopic methods, including UV, IR, HR-ESI-MS, and 1D and 2D NMR. The In-vitro anti-proliferative activities of all the compounds against two human cancer cell lines (SW982 and A549) were evaluated by CCK-8 assay. Compounds 1 and 4 showed medium anti-proliferative activity against SW982 cells, with IC 50 values of 3.49 ± 0.10 and 6.42 ± 1.23 μM, respectively. Additionally, compounds 2 , 7 , and 8 exhibited medium anti-proliferative activity against A549 cells, with IC50 values ranging from 0.80 ± 0.05 to 6.60 ± 0.46 μM. [Display omitted] [ABSTRACT FROM AUTHOR]

Nine polyacetylenes, including five new compounds named sadivaethynes E -I (1 – 5), were isolated from the roots of Saposhnikovia divaricata. Structural elucidation of compounds 1 – 5 was established by extensive spectroscopic analysis, quantum chemical calculations and DP4+ probability analysis. Among them, the absolute configuration of compound 1 – 2 , 4 – 5 was unambiguous determined by ECD. Also, all compounds were evaluated for cytotoxicity against two human cancer cell lines (A549, HEPG2) in vitro, compound 9 showed moderate inhibitory effect with an IC 50 value of 11.66 μM against HEPG2. [Display omitted] • Five undescribed compounds were isolated from the roots of Saposhnikovia divaricata. • The structures were characterized chemically by NMR, quantum chemical calculations and CD data analysis. • Compound 9 showed moderate inhibitory effect with an IC 50 value of 11.66 μM against HEPG2. [ABSTRACT FROM AUTHOR]

Triptolide exhibits superior and broad-spectrum antitumor activity. However, the narrow safety window caused by the toxicity of triptolide limits its clinical applications. Although several characterized targets for triptolide are reported, the association between triptolide and its targets in cancer therapy is not fully understood. Here, we show that acute myeloid leukemia (AML) cell lines are sensitive to triptolide by constructing an in vitro cell and in vivo xenograft models. Meanwhile, the triptolide-induced hepatotoxicity increases with increasing dosages within the xenograft models. Additionally, the expression levels of WSTF-RPB1 are strongly associated with the sensitivity to triptolide in hematological cancer cells and can be downregulated in a dose and time-dependent manner. Finally, we show that optimizing dosing regimens can achieve the same pharmaceutical effect and reduce toxicity. In summary, this study aims to search for triptolide-sensitive cell lines as well as the underlying molecular mechanisms in order to broaden the safety window of triptolide; thus, increasing its clinical utility. [ABSTRACT FROM AUTHOR]

To investigate the effects of transmembrane protein 45A (TMEM45A) on biological characteristics and cisplatin (DDP) resistance of cervical cancer cells. TMEM45A in cervical cancer cells and normal cervical epithelial cells (HCerEpiC) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. HPV genotypes were identified by multiplex PCR. SiHa and HeLa cells were divided into Blank, shCTL, shTMEM45A-1, and shTMEM45A-2 groups, followed by Cell Counting Kit-8 (CCK-8), EdU, Annexin V-FITC/PI staining, Wound healing, and Transwell invasion assays, as well as qRT-PCR and Western blotting. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) was employed to evaluate the impact of TMEM45A shRNA on cisplatin-resistant cervical cancer cells (SiHa/DDP and HeLa/DDP). Compared with HcerEpic cell, cervical cancer cells exhibited the upregulation of TMEM45A expression, especially in HPV-positive cell lines (CaSki, SiHa, HeLa). TMEM45A shRNA suppressed the proliferation of SiHa and HeLa cells, arrested cells at the S phase, and promoted cell apoptosis. TMEM45A shRNA inhibited the epithelial-mesenchymal transition (EMT), invasion, migration of SiHa and HeLa cells, accompanying by the downregulated Vimentin and N-cadherin with the upregulated E-cadherin. Moreover, SiHa/DDP and HeLa/DDP had higher TMEM45A expression than their parental SiHa and HeLa cells, respectively. And inhibiting TMEM45A can reduce the IC50 of SiHa/DDP cells and HeLa/DDP cells to cisplatin. Silencing TMEM45A can inhibit cell proliferation, invasion, migration and EMT, regulate cell cycle distribution, promote cell apoptosis, and reverse cisplatin resistance of HPV-positive cervical cancer cells, highlighting that inhibition of TMEM45A may be a therapeutic strategy for HPV-positive cervical cancer. [ABSTRACT FROM AUTHOR]

Seven new glycosides (1–7) and seventeen known analogues (8–24) were isolated from the leaves of Datura metel L. The structures of these compounds were all elucidated by detailed spectroscopic analyses and comparison with literature values. All isolates were evaluated for cytotoxicity against Hela, MGC-803, Ishikawa cell lines and compounds 6, 7, 14–17 and 24 exhibited different degrees of antiproliferative effects. [ABSTRACT FROM AUTHOR]

Isodon lophanthoides var. gerardianus (Benth.) H. Hara, a native medicinal plant produced chiefly across Southern China, is one of the mainstream varieties of Xihuangcao, which has long been applied in preventing and treating some common liver or gall diseases. Water-soluble total flavonoids (WSTF) extracted from folk herbal medicine have many pharmacological effects. The objective of the paper is to investigate the synergy of WSTF with 5-fluorouracil (5-FU) on HCC and the related mechanisms. Cells were exposed to WSTF alone or combination treatment with 5-FU. Then, in this study, we conducted cell viability test, cell cycle and clone forming test, apoptosis assay, reactive oxygen species (ROS), Western blotting, immunohistochemistry, and a xenograft tumor growth model for investigating the role of WSTF in HCC in vivo and in vitro. It was discovered that WSTF caused cell cycle arrest at the G0/G1 phase while increasing the ROS contents. The generation of ROS levels could cause cell apoptosis and inhibit colony formation. WSTF decreased the Bcl-2 level but promoted the Bax level. These showed the mitochondrial dependence of WSTF-mediated apoptosis. WSTF combined with 5-FU have a synergistic effect to significantly inhibit carcinogenicity in vivo and in vitro. The reduced ROS changed the synergy of WSTF with 5-FU. At last, WSTF inhibit the growth of HCC and promote the HCC sensitivity to 5-FU through ROS accumulation. WSTF-increased ROS levels may partially or completely contribute to enhanced toxicity. WSTF combined with 5-FU in HCC can play a synergistic effect when applied in the clinical setting. [ABSTRACT FROM AUTHOR]

Overexpressed gastrin is reported to promote oncogenesis and development of gastric cancer by inhibiting apoptosis of cancer cells; however, the underlying mechanism remains unclear. Our study is aimed at revealing the mechanism underlying the effect of gastrin on apoptosis of gastric cancer cells. Gastrin-interfering cell line was constructed by stably transfecting gastrin-specific pshRNA plasmid to gastric cancer cell line BGC-823. Then, differentially expressed proteins between untreated BGC-823 and gastrin-interfering BGC-823 cell lines were detected by the iTRAQ technique. GO and KEGG analysis was used to analyze the differentially expressed genes that code these differentially expressed proteins. The Annexin V-FITC staining assay was used to detect gastric cancer cell apoptosis. The DCFH-DA fluorescent probe staining assay was used to measure intracellular ROS. Mitochondrial membrane potential was detected by flow cytometry. Western blot was used to analyze the mitochondria respiratory chain proteins and apoptosis-related proteins. A total of 107 differentially expressed proteins were identified by iTRAQ. GO and KEGG analysis showed that proteins coded by the corresponding differentially expressed genes were mainly enriched in the mitochondrial oxidative respiratory chain, and the expression of three proteins (COX17, COX5B, ATP5J) was upregulated. The three proteins with higher scores were verified by Western blot. The apoptosis rate of the gastrin knockdown cancer cell was significantly increased; meanwhile, gastrin knockdown leads to increase of membrane potential and decrease of intracellular ROS production. Additionally, Bax was significantly increased, whereas NF-κB-p65 and Bcl-2 were downregulated after knockdown of gastrin. Concomitantly, pretreatment with NAC reversed the effect of gastrin on the Bax and Bcl-2 expression. Gastrin promotes the production of ROS from mitochondria, activates NF-κB, and inhibits apoptosis via modulating the expression level of Bcl-2 and Bax. [ABSTRACT FROM AUTHOR]

The extract of Broussonetia papyrifera has been proved to have antitumor activity. However, the underlying mechanism remains unclear. This study aimed to elucidate the mechanism of apoptosis of HepG2 cells induced by polyphenols from Broussonetia papyrifera (PBPs). The results revealed that PBPs inhibited the proliferation of HepG2 cells in a dose-dependent and time-dependent manner. Flow cytometry analysis showed that PBPs increased the apoptosis ratio of HepG2 cells significantly. PBPs increased intracellular reactive oxygen species (ROS) production and decreased intracellular superoxide dismutase (SOD) level of HepG2 cells. PBPs induced cell cycle arrest at G1 phase. Western blotting showed that PBPs upregulated the ratio of Bax/Bcl-2 and the expression level of Caspase-3, and activated p53 in HepG2 cells. The inhibition of proliferative relative signals (protein kinase B, PKB/AKT) and survival relative signals (extracellular signal-regulated kinase, ERK) were also observed in PBP-treated HepG2 cells. Our findings suggest that apoptosis of HepG2 cells induced by PBPs is mitochondria-mediated via inactivation of ERK and AKT signaling pathways. [ABSTRACT FROM AUTHOR]

In this study, we investigated the protective effects of genistein against SH-SY5Y cell damage induced by β-amyloid 25-35 peptide (Aβ25-35 ) and the underlying mechanisms. Aβ-induced neuronal death, apoptosis, glutamate receptor subunit expression, Ca2+ ion concentration, amino acid transmitter concentration, and apoptosis-related factor expression were evaluated to determine the effects of genistein on Aβ-induced neuronal death and apoptosis. The results showed that genistein increased the survival of SH-SY5Y cells and decreased the level of apoptosis induced by Aβ25-35 . In addition, genistein reversed the Aβ25-35 -induced changes in amino acid transmitters, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors, and N-methyl-d-aspartate (NMDA) receptor subunits in SH-SY5Y cells. Aβ25-35 -induced changes in Ca2+ and B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) protein and gene levels in cells were also reversed by genistein. Our data suggest that genistein protects against Aβ25-35 -induced damage in SH-SY5Y cells, possibly by regulating the expression of apoptosis-related proteins and Ca2+ influx through ionotropic glutamate receptors. [ABSTRACT FROM AUTHOR]

A new sesquiterpenoid glycoside, consisting of one vetispirane-type, dmetelisproside A (1), together with two known megastigmane sesquiterpenoids, citroside A (2) and staphylionoside D (3) were isolated from the leaves of Datura metel L. The structures were determined by analysis of their MS and NMR data as well as by comparison with literature values. All isolates were evaluated for cytotoxicity toward SGC-7901, Hepg2, HeLa, MCF-7, and MDA-MB-231 cancer cell lines, and anti-inflammatory activity against nitric oxide (NO) in RAW 264.7 cells in vitro. Compounds 1 and 2 exhibited pronounced cytotoxicity against SGC-7901 and HeLa cells with IC50 values in the range of 21.43 to 29.51 μm. All three compounds displayed potential effects against NO production with IC50 values of 31.10, 34.25, and 44.31 μm, respectively. Thus, these isolated compounds in the leaves of Datura metel L were subjected to bioactivity substances for future studies on medicinal application. [ABSTRACT FROM AUTHOR]

Purpose. The research aimed to identify the active component from Punica granatum L. to alleviate ischemia/reperfusion injury and clarify the underlying mechanism of the active component alleviating ischemia/reperfusion injury. Materials and Methods. The SH-SY5Y cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) was established to simulate the ischemia/reperfusion injury. According to the strategy of bioassay-guided isolation, the active component of punicalin from Punica granatum L. was identified. Flow cytometry and Western blotting were employed to evaluate the effects of OGD/R and/or punicalin on cell cycle arrest. Immunofluorescence assay was applied to assess the nucleus translocation. The relative content of ROS and GSH and the enzyme activities of CAT and SOD were examined using ELISA. Results. The data of bioassay-guided isolation showed that punicalin from Punica granatum L. could alleviate OGD/R-induced cell injury in SH-SY5Y cells. Flow cytometry analysis and Western blotting for probing the expression of CDK1, p-CDK1, cyclin B1, and p21 revealed that punicalin could relieve OGD/R-induced cell cycle G0/G1 arrest. Additionally, immunofluorescence assay and Western blotting for probing the expression of TGF-β and p-Smad2/p-Smad3 showed that punicalin could relieve the OGD/R-induced TGF-β/Smad pathway. Furthermore, the TGF-β/Smad pathway inhibitor of LY2157299 was employed to confirm that the TGF-β/Smad pathway is crucial to the effect of punicalin. At last, it was indicated that punicalin could relieve OGD/R-induced oxidative stress. Conclusion. Punicalin, an active component from Punica granatum L., was identified as a protective agent to alleviate the OGD/R-induced cell injury, which could exert the protective effect via TGF-β/Smad pathway-regulated oxidative stress and cell cycle arrest in SH-SY5Y cells. [ABSTRACT FROM AUTHOR]

The cytotoxicity of isosteviol and its twenty derivatives on three human tumor cell lines (ECA-109, MCF-7 and B16-F10) were evaluated. The results demonstrated that ECA-109 was the most sensitive cell line which was exposed to the compound (VI) with the lowest IC50 value of 1.30 ± 0.11 μM. By quantitative structure–activity relationship (QSAR) technique, the obtained cytotoxicity data were further utilized to respectively generate the statistically reliable HQSAR model (q2 = 0.828, r2 = 0.941, = 0.849) and topomer CoMFA model (q2 = 0.608, r2 = 0.919, = 0.747), which could provide the guidelines for the further development of novel and potent anti-esophageal agent. [ABSTRACT FROM AUTHOR]

The new natural products reported in 2019 in peer-reviewed articles in journals with good reputations were reviewed and analyzed. The advances made by Asian research groups in the field of natural products chemistry in 2019 were summarized. Compounds with unique structural features and/or promising bioactivities originating from Asian natural sources were discussed based on their structural classification. [ABSTRACT FROM AUTHOR]

The regulatory effect of luteolin on the progression of Alzheimer's disease (AD) remains unclear from the perspective of apoptosis. The present study aimed to investigate the protective effects of luteolin against Aβ25-35-induced cell apoptosis in pheochromocytoma (PC-12) cells. Aβ25-35 was used to induce an in vitro model of AD. Estradiol was used as a positive control. The PC-12 cells were incubated with luteolin alone or in combination with fulvestrant or U0126. The results showed that luteolin treatment significantly prevents Aβ25-35-induced decrease in cell viability and inhibits Aβ25-35-induced cell apoptosis. After the addition of fulvestrant and U0126, the apoptosis rate of PC-12 cells increased significantly. In addition, luteolin treatment significantly upregulated the expression of Bcl-2 and downregulated the expression of Bax and caspase-3, whereas fulvestrant and U0126 partially reversed the effects of luteolin. Moreover, luteolin treatment upregulated the expression of ERβ and p-ERK1/2, whereas fulvestrant blocked the expression of p-ERK1/2. The study showed that luteolin could activate the ER/ERK/MAPK signalling pathway to protect PC-12 cells against Aβ25-35-induced cell apoptosis via selectively acting on ERβ. Thus, luteolin may be considered as a potential novel therapeutic strategy for AD. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer (TNBC), in part because of the high metastasis rate, is one of the most prevalent causes of malignancy-related mortality globally. Ubiquitin specific peptidase 6 N-terminal like (USP6NL) has been unmasked to be implicated in some human cancers. However, the precise biological function of USP6NL in TNBC has not been defined.Methods: RNA expression was examined by real-time quantitative PCR (RT-qPCR), while USP6NL protein level was tested through western blot. Besides, cell proliferation was assessed by using colony formation assay, whereas cell apoptosis estimated by flow cytometry analysis, JC-1 assay and TUNEL assay. Transwell assays were adopted to detect the migration and invasion of indicated TNBC cells. Immunofluorescence (IF) assay evaluated epithelial-mesenchymal transitions (EMT) progress in TNBC. Further, RNA immunoprecipitation (RIP), RNA pull down and luciferase reporter assays were implemented for measuring the mutual interplay among USP6NL, miR-142-3p and long intergenic non-protein coding RNA 689 (LINC00689).Results: Elevated USP6NL level was uncovered in TNBC cells. RNA interference-mediated knockdown of USP6NL inhibited TNBC cell growth, motility and EMT. Further, USP6NL was proved as the target of a tumor-inhibitor miR-142-3p, and LINC00689 augmented USP6NL expression by absorbing miR-142-3p. Importantly, miR-142-3p deficiency or USP6NL overexpression fully abolished the inhibitory effect of LINC00689 silence on TNBC cellular behaviors.Conclusion: All data revealed the important role of USP6NL/LINC00689/miR-142-3p signaling in TNBC. The findings might provide a new and promising therapeutic biomarker for treating patients with TNBC. [ABSTRACT FROM AUTHOR]

A phytochemical investigation on the stems of Mappianthus iodoides led to the isolation of a new naturally occurring prenylated isoflavone, mappianthone A (1), together with seven known analogues (2−8). The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparison with data reported in the literature. All isolated compounds were evaluated for their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1−8 showed significant antiproliferative effects against several human cancer cell lines with IC50 values ranging from 0.16 to 12.68 μM. [ABSTRACT FROM AUTHOR]

Purpose: The cancer-testis antigen, which is a preferentially expressed antigen of melanoma (PRAME), is an ideal target for immunotherapy and cancer vaccines. Since the expression of this antigen is relevant to therapy responses, the heterogeneity in its expression and the underlying mechanism need to be investigated. Patients and Methods: Plasma cell sorting was performed in 48 newly diagnosed multiple myeloma (MM) patients. Real-time quantitative PCR was performed to examine the PRAME transcript levels and gene copy numbers. Bisulfate clone sequencing of the PRAME promoter and exon 1b regions was performed in 4 patients. Quantitative methylation-specific PCR of the +287 CpG site was performed for all patients. The human MM cell lines RPMI8226, LP-1 and MOLP-2 were treated with 5-azacytidine. Results: The median PRAME transcript level was 3.1% (range: 0– 298.3%) in the plasma cells sorted from the 48 MM patients. Eleven (22.9%) and 37 (77.1%) patients were individually categorized into the PRAME low- and high-expression groups according to the cut-off value of 0.05%. The methylation ratios of the promoter and the 3ʹ region of exon 1b region were both negatively related to the transcript levels. The degrees of methylation at the +287 CpG site were significantly negatively related to the transcript levels in all 48 patients (r=− 0.44, P=0.0018), and those in the high-expression group (r=− 0.69, P< 0.0001) but not those in the low-expression group (r=− 0.27, P=0.43). All 5 patients with homozygous deletions were categorized into the low-expression group. There were no significant differences in the PRAME transcript levels between the hemizygous deletion (n=8) and no deletion (n=35) groups (P=0.40). Furthermore, the PRAME transcript levels significantly increased in the MM cell lines after treatment with 5-azacytidine. Conclusion: Both methylation and copy number variation may participate in the regulation of PRAME expression in MM; in patients with no homozygous deletion, PRAME expression is mainly controlled by methylation, and a proportion of fairly low expression is caused by homozygous deletion. [ABSTRACT FROM AUTHOR]

Five new α-tetralone glycosides, juglanbiosides A-E (1–5), together with an α-tetralone derivative (15) and nine known 1,4-naphthoquinones (6–14) were isolated from the 95% EtOH extract of green walnut husks of Juglans mandshurica Maxim. Their structures were elucidated by comprehensive spectroscopic methods (1H, 13C NMR, DEPT, HSQC, HMBC, CD, HR-ESI-MS). In vitro cytotoxicities of all the isolated compounds were evaluated against BGC-823, HCT-15 and K562 cancer cell lines. [ABSTRACT FROM AUTHOR]

A new naturally occurring trinoreudesmane sesquiterpene, artahongkongol A (1), together with seven known eudesmane sesquiterpenes (2−8), was isolated from the stems and leaves of Artabotrys hongkongensis Hance. Among them, 1 is a rare trinoreudesmane sesquiterpene containing 12 carbon atoms on the carbon skeleton. All known compounds (2−8) were isolated from the genus Artabotrys for the first time. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with data reported in the literature. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1−8 showed significant inhibitory effects against various human cancer cell lines with IC50 values ranging from 0.57 to 15.68 μM. [ABSTRACT FROM AUTHOR]

Aptamers which are promising and effective molecular probes, can deliver either fluorescent materials or radionuclides to tumors. This study aimed to develop a novel both fluorescent and radionuclide dual-modality probe based on a truncated aptamer and evaluate its stability and binding affinities in vitro. The aptamer JHIT2 with binding specifically to HepG2 cells was previously generated by Cell-SELEX. Using mfold and RNAstructure software to predict the secondary structure folded by a middle random sequence to truncate the primer sequences at both ends of the aptamer JHIT2 to yield the aptamer JHIT2e, with a similar secondary structure to JHIT2 and the same specificity and affinity as JHIT2. Attaching carboxyfluorescein (FAM) readily to the aptamer JHIT2e and then attaching iodine-131 to the FAM moiety which has multiple sites for iodine labeling to develop a novel both fluorescent and radionuclide dual-modality probe, termed 131I-FAM-JHIT2e. Cell uptake and fluorescence imaging assays in vitro confirmed that 131I-FAM-JHIT2e had both FAM fluorescence signal and radio-activity signal and maintained specific binding ability to the human hepatoma cell line HepG2. This work formed a basis for aptamer-based, dual-modality imaging probe that contains both fluorescent and radionuclide tags, which also is potential for theranostics. Image 1 • Truncating the primer sequences at both ends of aptamer JHIT2 to yield JHIT2e. • JHIT2e has the same specificity and affinity as JHIT2. • 131I-FAM-JHIT2e was prepared by attaching iodine-131 to FAM of FAM-JHIT2e. • 131I-FAM-JHIT2e has both FAM fluorescence and radio-activity signal. • 131I-FAM-JHIT2e has specific binding ability to HepG2 cells. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the roots of Solanum melongena L. resulted in the isolation of ten terpenes and sixteen lignans, including a new triterpene saponin, officinoterpenoside E (1) and twenty-five known compounds (2-26). All compounds were firstly isolated from S. melongena except 2, 13, 21, 22. The structures of these compounds were determined by 1 D and 2 D NMR spectra referring to the literatures, together with high-resolution mass spectrometric analysis. All compounds were evaluated for the cytotoxicity against three cancer cell lines (HepG2, Hela, and MCF-7) in vitro. The results showed that compounds 1, 6, 20, 25 and 26 exhibited moderate cytotoxicity against HepG2, Hela and MCF-7 cells with IC50 values in the range of 16.8 ± 1.7 to 29.1 ± 1.9 μM. Therefore, these terpenoids and lignans may have potential biological activity, and also seemed to be of great chemotaxonomic value for S. melongena. [ABSTRACT FROM AUTHOR]

A phytochemical investigation on the stems and leaves of Clausena emarginata led to the isolation of a previously undescribed carbazole alkaloid, clausemargine A (1), together with 11 known analogues (2–12). The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with data reported in the literature. All known compounds (2–12) were isolated from C. emarginata for the first time. All isolated compounds were evaluated for their their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1–12 showed significant antiproliferative effects with IC50 values ranging from 0.28 to 15.18 μM. [ABSTRACT FROM AUTHOR]

Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen species (ROS) production, and apoptosis induction in imatinib-resistant CML K562/G01 cells and explored their potential mechanisms. Stable K562/G01 cells with knockdown of Nrf2 were established by infection of siRNA-expressing lentivirus. The mRNA and protein expression levels of Nrf2 and TrxR were determined by real-time quantitative polymerase chain reaction and western blot, respectively. ROS generation and apoptosis were assayed by flow cytometry, while drug sensitivity was measured by the Cell Counting Kit-8 assay. Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells at both mRNA and protein levels. Expression levels of Nrf2 and TrxR were positively correlated in K562/G01 cells. Knockdown of Nrf2 in K562/G01 cells enhanced the intracellular ROS level, suppressed cell proliferation, and increased apoptosis in response to imatinib treatments. Nrf2 expression contributes to the imatinib resistance of K562/G01 cells and is positively correlated with TrxR expression. Targeted inhibition of the Nrf2-TrxR axis represents a potential therapeutic approach for imatinib-resistant CML. [ABSTRACT FROM AUTHOR]

Objective: To characterize the molecular mechanism underlying the antineoplastic activity of Celastrus orbiculatus Thunb. extracts (COE). Methods: The human hepatocellular carcinoma HepG2 cells with mammalian target of rapamycin (mTOR) knockdown expressed (HepG2/mTOR) were constructed using molecular biological technology. In vitro, the HepG2/mTOR− cells were treated with COE at various concentrations (10, 20, 40, 80, 160 and 320 µ g/mL). Cell viability was determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. According to the half-maximal inhibitory concentration (IC50) value (140 mg/L), the concentrations of COE in the subsequent experiment was set to alleviate cytotoxicity. The HepG2/mTOR− cells were divided into 5 groups: negative control (untreated), COE treatment groups (40, 80, 120 mg/L COE) and positive control group (cisplatin, DDP, 2 mg/L), respectively. Wild-type HepG2 cells were used as a blank control. The effects of COE on the cell apoptosis were analyzed by flow cytometry and transmission electronic microscopy (TEM), respectively. The protein expression levels of mTOR signal pathways were determined by Western blotting. In vivo, HepG2/mTOR− cells (2 × 106 cell/mice) were subcutaneously injected into the right flank of nude mice. Thirty-six female nude mice were randomly assigned to 6 groups according to body weight (6 mice per group) as follows: solvent vehicle control, Banmao Capsule treated group (BM, 195 mg/kg), Tegafur, Gimeracil and Oteracil Potassium Capsules (10 mg/kg) treated group, and different dosages of COE (10, 20, 40 mg/kg) groups. Tumor growth was monitored and immunohistochemical staining was used to examine the expression of apoptosis-related proteins in tumor tissues. Results: COE inhibited the proliferation significantly in a concentration-dependent manner in HepG2/mTOR− cells (P<0.01). COE significantly induced the apoptosis of HepG2/mTOR− cells (P<0.01), and the apoptotic bodies can be observed under TEM. COE significantly inhibits the proteins expression of mTOR-related signal pathways. In vivo, COE significantly inhibited tumor growth in nude mice (P<0.01). Moreover, the results showed that COE down-regulated the expression of Bcl-2 and Bcl-xL, and up-regulated the levels of Bax and caspase-3 protein (P<0.01). Conclusion: COE was a potential chemotherapeutic drug in HCC treatments via targeting mTOR signal pathway. [ABSTRACT FROM AUTHOR]

Two new tetralone glycosides, 4(S)-5-methoxy juglanoside A (1), 4(S)-5-methoxy juglanoside D (2), together with ten known compounds (3–12) have been isolated from the green walnut husks of Juglans mandshurica Maxim. Their structures were elucidated on the basis of their ESI-MS, 1 D and 2 D NMR spectroscopic data. In addition, all compounds were evaluated for their cytotoxic activities against the cancer BGC-823 (human gastric carcinoma), HCT-15 (human colorectal carcinoma) and K562 (human chronic myeloid leukemia) cell lines. The results showed aglycones of naphthoquinones had stronger cytotoxic activities than glycosides of tetralone. [ABSTRACT FROM AUTHOR]

A phytochemical investigation on the stems and leaves of Clausena lenis led to the isolation of a new furanocoumarin, clauselenisin A (1), together with five known analogues (2–6). The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with data reported in the literature. All known compounds (2–6) were isolated from C. lenis for the first time. All isolated compounds were evaluated for their their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1–6 showed significant antiproliferative effects with IC50 values ranging from 0.36 to 16.48 μM. [ABSTRACT FROM AUTHOR]

Treatment strategies involving tyrosine kinase inhibitors (TKIs) for patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations have advanced significantly; however, challenges still remain regarding the development of resistance. It has been reported that receptor tyrosine kinase-like orphan receptor 1 (ROR1) acts as a hepatocyte growth factor receptor (MET) and c-Src substrate, and that the extracellular domain of ROR1 is associated with EGFR to sustain EGFR-ERBB3-PI3K signaling. Our previous study reported that blocking ROR1 significantly decreased the activity of key signal molecules in the AKT/mammalian target of rapamycin (mTOR) signaling pathway, which was associated with a significant increase of apoptosis and significant decrease of proliferation of lung adenocarcinoma cells. The present study hypothesized that inhibiting ROR1 could potentially prevent erlotinib resistance in NSCLC cell lines. Investigations were performed with two erlotinib-resistant cell lines XLA-07 and NCI-H1975, and an erlotinib-acquired-resistant cell line PC-9erlo, which was developed from its parental cell line PC-9. It was identified that the inhibition of ROR1 via small interfering RNA treatment significantly improved the anti-proliferation and apoptosis-inducing roles of erlotinib in TKI-resistant tumor cells. This was in accordance with the activity of key molecules of the AKT/mTOR signaling pathway, including glycogen synthase kinase-3α/β (GSK-3α/β), phosphatase and tensin homolog (PTEN), AKT, mTOR and ribosomal protein S6 kinase β-1 (p70S6K). The current data suggest that targeting ROR1 is a potential novel treatment strategy for patients with ROR1-positive NSCLC, particularly those with acquired resistance to EGFR-TKI. [ABSTRACT FROM AUTHOR]

Summary: Refinement of risk stratification in Philadelphia chromosome (Ph)‐negative B‐cell acute lymphoblastic leukaemia (ALL) might aid the identification of patients who are likely to relapse. Abnormal S100 calcium binding protein A16 (S100A16) has been implicated in various cancers, but its function remains unclear. We found S100A16 transcript levels were higher in 130 adults with newly‐diagnosed Ph‐negative B‐cell ALL compared with 33 healthy controls. In 115 of 130 patients who achieved first complete remission, those with high S100A16 transcript levels displayed a lower 3‐year cumulative incidence of relapse (CIR; 34% [21, 47%] vs. 40% [48, 72%]; P = 0·012) and higher 3‐year relapse‐free survival (RFS; 65% [53, 78%] vs. 35% [23, 46%]; P = 0·012), especially when receiving chemotherapy only. In multivariate analysis a low S100A16 transcript level was independently‐associated with a higher CIR (Hazard ratio [HR] = 3·74 [1·01–13·82]; P = 0·048) and inferior RFS (HR = 5·78 [1·91, 17·84]; P < 0·001). Function analysis indicated that knockdown of S100A16 promoted proliferation and anti‐apoptosis and reduced chemosensitivity. S100A16 over‐expression revealed an opposite trend, especially in a xeno‐transplant mouse model. Western blotting analysis showed upregulation of PI3K/AKT and ERK1/2 in S100A16‐knockdown and S100A16‐overexpression B‐cell ALL cell lines respectively. Inhibition assays suggested these two signalling pathways participated in the S100A16‐mediated proliferation and survival effects in B‐cell ALL cell lines. Trial Registration: Registered in the Chinese Clinical Trial Registry [ChiCTR‐OCH‐10000940]; http://www.chictr.org.cn. [ABSTRACT FROM AUTHOR]

Abstract We report here the synthesis, characterization of seventeen (E)-2-methyl-3-ferrocenyl- N -acrylamides. The single crystal structures of the key intermediate b and two target compounds d5 and d6 were confirmed by X-ray crystallographic analysis. Antitumor activity of all compounds was tested in vitro. Compound d1 was the most significant one against B16 F10 cell line, indicating that it could be a good candidate for further study. Furthermore, cancer cell apoptosis assay was performed and the result indicated that compound d1 effectively fueled B16 F10 cells apoptosis in a dose-dependent manner. Graphical abstract Image 1 Highlights • Total seventeen (E)-2-methyl-3-ferrocenyl- N -acrylamides were synthesized. • Compounds b , d5 and d6 were confirmed by X-ray crystallographic diffraction. • d1 exhibited significant antitumor activity and effectively fueled cells apoptosis. [ABSTRACT FROM AUTHOR]

Eight new iridoids (1–8) and an ionone glucoside (9), together with 31 known compounds (10–40), were isolated from the whole plants of Rehmannia henryi. The structures of these compounds were elucidated on the basis of their spectroscopic data and chemical evidence. [ABSTRACT FROM AUTHOR]