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Title: | Investigation of the synergistic effects of paclitaxel and herbal substances and endemic plant extracts on cell cycle and apoptosis signal pathways in prostate cancer cell lines | Authors: | Doğan Şiğva, Z.Ö. Balci Okcanoğlu, T. Biray Avci, Ç. Yilmaz Süslüer, S. Kayabaşi, Ç. Turna, B. Dodurga, Yavuz |
Keywords: | Apoptosis Cell cycle Endemic plant extracts’ Herbal substances Paclitaxel Prostate cancer cell lines lipocortin 5 paclitaxel plant extract protein Bax protein bcl 2 silymarin antineoplastic agent isothiocyanic acid derivative sulforafan animal cell apoptosis Article cell cycle cell cycle arrest cell cycle G2 phase cell cycle M phase drug potentiation ED50 gene expression IC50 nonhuman priority journal prostate cancer cell line TUNEL assay Boraginaceae cell proliferation chemistry combination drug therapy drug effect human male pathology Phlomis prostate tumor Rubiaceae signal transduction tumor cell culture Antineoplastic Agents, Phytogenic Cell Cycle Cell Proliferation Drug Synergism Drug Therapy, Combination Humans Isothiocyanates Male Plant Extracts Prostatic Neoplasms Signal Transduction Silymarin Tumor Cells, Cultured |
Publisher: | Elsevier B.V. | Abstract: | Paclitaxel, which isolated from Taxus brevifolia, is recently started to be used against prostate cancer treatment and it is a very effective compound against cancer. In this study, we aimed to test the synergistic effect of two plant active compounds (sulphoraphane (SFN) and silymarin (SILY)) and several endemic plant species from Turkey (such as Phlomis leucophracta, Rubia davisiana, Alkanna tinctoria), which are known to have anticarcinogenic effect on androgen-independent PC3 and DU145, and androgen-dependent VCaP prostate cancer cell lines, with paclitaxel on the expression of cell cycle signaling and apoptosis regulator genes. Herbal substances and endemic herbal extracts were combined with Paclitaxel drug. IC50 doses were identified as real-time online. The most effective synergistic doses were determined according to isobologram analysis. The apoptotic effects of effective combined doses were evaluated by TUNEL, Annexin V, and JC-1 methods. Apoptotic and/or cell cycle arrest effects of confirmed combined doses on the expression of genes in these pathways were assessed by real-time online. Endemic plant extracts (Alkanna tinctoria, Phlomis leucophracta and Rubia davisiana, IC50 < 220 µg/ml) and herbal substances (SILY, and SFN IC50 < 130 µM) indicated antiproliferative and apoptotic effects in prostate cancer cell lines. They testified to the synergistic effect of paclitaxel with endemic plant extracts (Combination Index CI, ED50 < 0.41). The combinations, which indicate the synergistic effect was increased to the Bax/Bcl-2 ratio by suppressing Bcl-2 gene expression into the prostate cancer cell lines. Besides, they increased the expression of TNFRSF10A, TNFRSF1A, CHEK1, CDKN1A, CDKN2B, CDK8, CDKN3 and CASP14 and decreased BAD, CDK5RAP1, CDC20, cyclin H, CDK5RAP1, CDC20. The effective doses of paclitaxel were reduced and G2/M arrest was induced by the endemic plant extracts and herbal substances that indicate a synergistic effect with paclitaxel. By using different combination of herbal extracts or active substances with paclitaxel, more economical and efficient treatment strategies can be developed. © 2018 Elsevier B.V. | URI: | https://hdl.handle.net/11499/30237 https://doi.org/10.1016/j.gene.2018.11.049 |
ISSN: | 0378-1119 |
Appears in Collections: | PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection Tıp Fakültesi Koleksiyonu WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection |
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