Abstract
Purpose: Prostate cancer is as far the most prevalent male cancer. Rutin (a glycoside from quercetin flavonoid) displays antioxidant activity leading to cell apoptosis. Combined effects of rutin with the widely used anti-cancer drug, 5-fluorouracil (5-FU), on prostate cancer cell line (PC3) was investigated herein. Methods: Different concentrations of combined 5-FU and rutin were applied to PC3 cells compared to separate treatment for 48 hours. Cell viability, as well p53 gene expression respectively were assessed by MTT assay and real-time quantitative polymerase chain reaction (qPCR). Changes of Bcl-2 signal protein and apoptosis were determined using western blot and flow cytometry procedures, respectively. Clonogenic assay was used to colony counts assessment. Results: 50% inhibitory concentration (IC50) of separate cell treatment with either rutin and 5-FU respectively were 900 μM and 3Mm, while combination index (CI) of combined 5-FU /rutin application reached a level of synergistic effects (0.33). Combination of 5-FU/rutin enhanced apoptosis and p53 gene expression in PC3 cells. PC3 cell colony counts and Bcl-2 signaling protein were decreased by 5-FU/rutin combination. Conclusion: Synergistic effects of 5-FU/rutin combination on PC3 cells line enhanced apoptosis, p53 gene expression, and down-regulation of Bcl-2 protein, compared to control separate application. 5-FU/rutin combination does seem an interesting therapeutic pathway to be further investigated.
Highlights
Prostate cancer represents the second widespread cancer and about 10% of all cancers in men.[1]
Rutin displays antioxidant activity leading to cell apoptosis
5-Fluorouracil (5-FU) is one of the chemotherapy agents widely used as anticancer treatment, especially in the setting of breast and prostate cancers[4]; yet, nausea, vomiting, mucositis, stomatitis, and diarrhea remains the major therapeutic side-effects.[5]
Summary
Prostate cancer represents the second widespread cancer and about 10% of all cancers in men.[1]. Combining anticancer drugs and antioxidant agents do enhance anticarcinogenic and anti-proliferative effects compared to chemotherapy alone.[13,14] Rutin and apigenin, as antioxidant agents, induce apoptosis in MCF-7 cancer cells through p53-dependent pathway, increasing anti-tumor activity of tamoxifen on cancer cells.[15]. Synergistic effects of anti-oxidant agents and chemotherapeutic drugs (such as combination of gemcitabine, 5-FU, and cisplatin) resort on induction of apoptosis, inhibition of cell proliferation and metastasis invasion.[16,17,18] Chemo-herbal combination therapy does attenuate the hazards to inducing drug resistance and prevalence of chemotherapy side effects.[19] The present study was designed to investigate the synergistic effects of rutin and 5-FU chemo-herbal combination on apoptosis, colony formation, p53 gene expression, and Bcl-2 signaling protein in PC3 prostatic cancer cells
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