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Copyright of Archives Medical Review Journal / Arsiv Kaynak Tarama Dergisi is the property of Cukurova University, Faculty of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The aim of this study was to synthesize chitosan nanoparticles loaded with rapeseed extract (RPE-CN) and to evaluate its therapeutic effects. The RPE-CNwas synthesized (Ion gelation), characterized (DLS, FTIR, atomic and electron microscopy) and their toxicity was evaluated by MTT method.Anti-inflammatory and pro-apoptotic effects were evaluated by qPCR method. Its antioxidant power was measured by ABTS, DPPH and FRAP methods and CAM method was used to evaluate its anti-angiogenic effects.Treatment with RPE-CN(Ps: 93.81 nm, PDI: 0.3, and ζ p: +35mv) reduced MCF7 cell viability and increased expression of genes associated with apoptosis (Caspase-3 and Caspase-9), inflammation (IL10) and antioxidant (SOD).RPE-CN exhibited notable inhibition in ABTS, DPPH, and Fe3+-TPTZ free radicals. Finally, angiogenesis in CAM tissue was suppressed by the down-regulation of VEGFR gene expression. According to the results, RPE-CN can be introduced as a potential chemo-preventive agent in the treatment of cancer. [ABSTRACT FROM AUTHOR]

Considering the great potential of natural products as anticancer agents, the present study was designed to explore the molecular mechanisms responsible for anticancer activities of Mesua ferrea stem bark extract against human colorectal carcinoma. Based on MTT assay results, bioactive sub-fraction (SF-3) was selected for further studies using HCT 116 cells. Repeated column chromatography resulted in isolation of less active α-amyrin from SF-3, which was identified and characterized by GC-MS and HPLC methods. α-amyrin and betulinic acid contents of SF-3 were measured by HPLC methods. Fluorescent assays revealed characteristic apoptotic features, including cell shrinkage, nuclear condensation, and marked decrease in mitochondrial membrane potential in SF-3 treated cells. In addition, increased levels of caspases-9 and −3/7 levels were also observed in SF-3 treated cells. SF-3 showed promising antimetastatic properties in multiple in vitro assays. Multi-pathway analysis revealed significant down-regulation of WNT, HIF-1α, and EGFR with simultaneous up-regulation of p53, Myc/Max, and TGF-β signalling pathways in SF-3 treated cells. In addition, promising growth inhibitory effects were observed in SF-3 treated HCT 116 tumour spheroids, which give a hint about in vivo antitumor efficacy of SF-3 phytoconstituents. In conclusion, these results demonstrated that anticancer effects of SF-3 towards colon cancer are through modulation of multiple molecular pathways. [ABSTRACT FROM AUTHOR]

Species of the Salvia genus are aromatic herbs and traditionally used for many medicinal purposes in Anatolia. The genus has produced an extraordinarily large number of beneficial secondary metabolites belonging to numerous chemical groups. Salvia pisidica is an endemic plant of southwest Anatolia, the dried parts of which are used as herbal tea and local materia medica. The composition of endemic S. pisidica essential oil was determined through GC-MS studies. In vitro cytotoxicity activity and apoptosis analysis were investigated by MTT assay, q-PCR and Annexin V staining experiments. Our results showed that 1,8 cineole (19.15 %) camphor (18.12 %) and γ-gurjunene (8.58 %) were the major constituents of the essential oil. It showed cytotoxic effects on the human breast cancer MCF-7, colon carcinoma Caco-2, hepatocyte carcinoma HepG2, and prostate carcinoma LnCap. The results of q-PCR and image-cytometer analysis showed that the essential oil caused induction of apoptosis by intrinsic and extrinsic pathways in all cancer cell lines. S. pisidica essential oil demonstrates considerable cytotoxic activity due to an apoptosis-related mechanism, suggesting that their bioactive components could be used as natural anticancer substances. [Display omitted] • Salvia pisidica esssential oil was cytotoxic and apoptotic in MCF-7, Caco-2, HepG2 and LnCap cells. • S. pisidica essential oil induced apoptosis via intrinsic pathway. • The esssential oil content was found different than previous studies. • The essential oil contains 1,8 cineole, camphor and γ-gurjunene as a major components. [ABSTRACT FROM AUTHOR]

Medicinal plants have been used in many countries for millennia as therapeutic agents for numerous diseases from diabetes to cancer. Gentiana plants are used in folk medicine to treat various diseases. This study mainly focuses on the vital pharmacological properties of ethanol extract of G. septemfida Pallas, including antioxidant, apoptotic, cytotoxic properties (in HT-29, human colorectal cell line) and phenolic compounds. Expression of apoptosis related genes (Bcl-2, Bid, Bax, caspase-3, caspase-7, caspase-8, caspase-9, caspase-10) in the apoptosis pathway were determined for apoptosis inducing activity. Additionally, we also evaluated the mineral composition (P, Ca, Mg, K, Fe, Mn, Zn, B and Cu) of G. septemfida Pallas. The ethanol extract showed antioxidant activities (phosphomolybdenum, 225.21 ± 6.95 mg/g; DPPH, IC 50: 581.7 ± 14 μg/mL; ABTS, IC 50: 217.11 ± 2.2 μg/mL) and also exhibited apoptotic and cytotoxic effects on the human colorectal cell line. The major phenolics were identified by HPLC were ferulic, ellagic and 4-hydroxybenzoic acid. G. septemfida Pallas is a potential source of anticancer agents for colon cancer treatments, and an alternative source of antioxidant agents for pharmacological applications. However, further research is required before such use could be proposed with confidence. [ABSTRACT FROM AUTHOR]

Drug resistance of colon cancer cells is the key to affect the efficacy of colon cancer chemotherapy and lead to chemotherapy failure. Recent studies have found that exosomes play an important role in chemoresistance of colon cancer, while the expression of VMP1 may be involved in exosome secretion. Drug sensitivity of colon cancer cells was detected by MTT. VMP1 expression levels were detected by qPCR and western blot. Expression of VMP1 was silenced in SW620 and HT-29 cell lines. Exosomes were isolated by ultracentrifugation, the particle size and concentration of exosomes were analyzed by NTA, and the morphology of exosomes was investigated by transmission electron microscopy. Exosome marker protein expression was detected by Western blot. The effect of exosomes on 5-FU sensitivity in SW620 and HT-29 cells was examined by MTT and western blot. VMP1 presented high expression in SW620 and HT-29 cells, their VMP1 gene and protein levels were significantly higher than those in SW480 and HCT116 cells, they were less sensitive to 5-FU, and exosome secretion was significantly reduced in SW620 and HT-29 cells after silencing of VMP1. Importantly, addition of exosomes to cells after silencing of VMP1 re-improved drug resistance. Co-incubation of exosomes secreted from SW620 and HT-29 cells with homologous cells significantly increased cell viability after 5-FU (50 μM) treatment, and increased the expression levels of the resistance protein ABCC1 and the anti-apoptotic protein Bcl-2. High expression of VMP1 in colon cancer cells is able to promote exosome secretion, which mediates the acquisition of more drug-resistant properties by cancer cells. • VMP1 is highly expressed in colon cancer cells. • VMP1 promotes exosome secretion. • VMP1 enhances 5-FU resistance. [ABSTRACT FROM AUTHOR]

Abstract: Alternative splicing plays an important role in gene expression by producing different proteins from a gene. Caspase-2 pre-mRNA produces anti-apoptotic Casp-2S and pro-apoptotic Casp-2L proteins through exon 9 inclusion or skipping. However, the molecular mechanisms of exon 9 splicing are not well understood. Here we show that knockdown of SRSF3 (also known as SRp20) with siRNA induced significant increase of endogenous exon 9 inclusion. In addition, overexpression of SRSF3 promoted exon 9 skipping. Thus we conclude that SRSF3 promotes exon 9 skipping. In order to understand the functional target of SRSF3 on caspase-2 pre-mRNA, we performed substitution and deletion mutagenesis on the potential SRSF3 binding sites that were predicted from previous reports. We demonstrate that substitution mutagenesis of the potential SRSF3 binding site on exon 8 severely disrupted the effects of SRSF3 on exon 9 skipping. Furthermore, with the approach of RNA pulldown and immunoblotting analysis we show that SRSF3 interacts with the potential SRSF3 binding RNA sequence on exon 8 but not with the mutant RNA sequence. In addition, we show that a deletion of 26nt RNA from 5′ end of exon 8, a 33nt RNA from 3′ end of exon 10 and a 2225nt RNA from intron 9 did not compromise the function of SRSF3 on exon 9 splicing. Therefore we conclude that SRSF3 promotes exon 9 skipping of caspase-2 pre-mRNA by interacting with exon 8. Our results reveal a novel mechanism of caspase-2 pre-mRNA splicing. [Copyright &y& Elsevier]

Abstract: During normal pregnancy trophoblastic debris is shed from the placenta into the maternal blood and endothelial cells may contribute to the phagocytosis of this material. Many researchers believe the majority of this trophoblastic material is apoptotic in normal pregnancy. Previously we demonstrated that phagocytosis of necrotic, but not apoptotic trophoblastic debris induced endothelial cell activation. In macrophages, phagocytosis of necrotic cell bodies leads to inflammation but phagocytosis of apoptotic bodies actively induces tolerogenic immune responses. We undertook this study to determine whether phagocytosis of apoptotic trophoblastic debris had a “tolerogenic” effect on endothelial cells analogous to their effect in macrophages. Apoptotic or necrotic trophoblastic debris was obtained from placental explants and endothelial cell activation was examined by quantifying, cell surface ICAM-1 expression using ELISAs, or monocyte adhesion. The response of endothelial cells to the activating stimuli of necrotic trophoblastic debris, interleukin-6 (IL-6), Lipopolysaccharide (LPS) or phorbol mysterate acetate (PMA) was reduced in endothelial cells that had phagocytosed apoptotic trophoblastic debris. This protective effect was short-lived being not apparent 24 h after removal of the trophoblastic debris. This work demonstrates that the ability of the endothelial cells to respond to a variety of activating stimuli is reduced by prior phagocytosis of apoptotic trophoblast debris. This might explain why endothelial cells are not activated by the small numbers of necrotic trophoblastic debris that may be found in normal pregnancy. This phenomenon may also contribute to the maternal vascular adaptation that occurs in normal pregnancy. [Copyright &y& Elsevier]

Background: Taxane drugs block cell-cycle progression via centrosomal impairment, induction of abnormal spindles, and suppression of spindle microtubule dynamics. Affected cells experience aberrant mitosis or mitotic slippage, which may trigger apoptosis. Objective: The aim was to characterize the histopathologic changes due to taxane therapy in skin biopsy specimens. Methods: Three examples were identified of benign skin biopsy specimens of patients receiving paclitaxel or docetaxel therapy for breast carcinoma or leiomyosarcoma. All specimens were studied by light microscopy after routine histopathologic processing. Results: All cases exhibited numerous apoptotic and mitotic figures including atypical forms, changes consistent with cytotoxic effects of taxane. The first case had been provisionally considered by the referring pathologist to be a malignant melanoma; however, when reviewed in consultation, it was ultimately diagnosed as an atypical nevus; the second and third cases were diagnosed as reactive epidermal hyperplasia and ecthyma, respectively, in addition to showing background taxane effects. Limitations: This study is limited by the relatively small number of cases examined. Conclusion: Taxane therapy has profound cytopathic effects in skin biopsy specimens, and in difficult cases these changes may raise consideration of possible malignancy. Dermatopathologists should use caution when interpreting biopsy specimens of patients receiving taxane therapy. [ABSTRACT FROM AUTHOR]

Abstract: Saponins are well known as plant stress-induced protective agents. Saponin compounds are also considered responsible for numerous pharmacological properties including anticarcinogenic activity. This paper evaluates the antiproliferative activity and mode of action of spirostane (SAP-1016 and SAP-884) and furostane (KE-1046 and KE-1064) saponins we have isolated from Balanites aegyptiaca Del. The compound SAP-1016 (3β-O-β-d-xylopyranosyl-(1–3)-β-d-glucopyranosyl-(1–4)-[α-l-rhamnopyranosyl-(1–2)]-β-d-glucopyranoside) showed potent antiproliferative activity against MCF-7 human breast cancer cells and HT-29 human colon cancer cells, with IC50 values of 2.4±0.35 and 3.3±0.19μM, respectively, compared with dioscin, one of the most potent cytotoxic spirostane saponins, with IC50 values of 3.1±0.39 and 4.9±0.32μM, respectively. Significant anti-proliferative activity of SAP-1016 was also observed compared to a well-known anticancer agent, cisplatin, against both MCF-7 human breast cancer cells and HT-29 human colon cancer cells. Additionally, significant selectivity of growth inhibition, between MCF-7 breast cancer cells and HFF normal cells, was detected with the furostane saponins. Treatments of HT-29 cells with 5μM SAP-1016 for 24h generated caspase-3 cleavage and therefore apoptosis activation. SAP-1016 also demonstrated reactive oxygen species (ROS) generation in both HT-29 and MCF-7 cancer cells in a time-dependent manner. [Copyright &y& Elsevier]

Lead (Pb), as a toxic heavy metal pollutant, has been paid much attention. Pb is often discharged into the environment through the soot, wastewater and waste residue in industrial production, which poses a great threat to animal health. Selenium (Se) is a trace element known to antagonize the toxicity caused by heavy metals. However, the interaction between Se and Pb in chicken kidney and its specific biological mechanism are still unclear. So, we constructed chicken models of Pb exposure and Pb, Se co-exposure. Therefore, we used western blot and qRT-PCR to detect the expression of related genes. The results showed that Pb activated the MAPK signaling pathway by up-regulating the expression of MARK pathway genes to induce the expression of pro-apoptotic genes and necroptosis-related genes. Se can regulate the MARK signaling pathway and attenuated the expression of MAPK pathway genes altered by Pb to reduce apoptosis and necroptosis of chicken kidney cells. Our study gives new ideas for the specific mechanism of Pb nephrotoxicity and provides a reference for comparative medicine and clinical medication. • Pb induces apoptosis and necrosis of chicken kidney cells through P38/JNK/ERK pathway. • Se antagonizes the toxic effect of Pb on chicken kidney. • Se antagonizes Pb-induced apoptosis and necrosis through P38/JNK/ERK pathway. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to examining the effect of high concentration of copper on the cell cycle and cell membrane potential of the primary hepatocyte in broilers. Topics discussed include the use of flow cytometry to measure cell cycle and cell membrane potential, the impact of high concentration of copper on relative fluorescence intesities, and the impact of copper concentration on apoptosis.