Please use this identifier to cite or link to this item: https://hdl.handle.net/11499/30237
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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