Synergetic Impact of Combined 5-Fluorouracil and Rutin on Apoptosis in PC3 Cancer Cells through the Modulation of P53 Gene Expression

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.

Does Bromelain-Cisplatin Combination Afford In-Vitro Synergistic Anticancer Effects on Human Prostatic Carcinoma Cell Line, PC3?

“…Seeking to overcome chemotherapy limitations, chemoherbal combinational treatment (CHCT) emerged as a potential solution by taking in advantage the inate anticancer properties of natural herbal medicine to chemotherapeutic agents. Rutin, curcumin, thymoquinone, ZnO nanoparticles and bromelain recently proved their potency to enhance cytotoxicity of chemotherapeutic agents on various human cell lines [7,10,13,[19][20][21]. Of recent, the synergistic or permissive anticancer potency of natural herbal products, reported by in-vitro investigations or animal models on human neoplastic cell lines, do provide new insights as to consider means and ways to modulate chemotherapy condut.…”

Mechanisms of Spica Prunellae against thyroid-associated Ophthalmopathy based on network pharmacology and molecular docking

“…Quercetin is a flavonoid phytoestrogen exhibiting antioxidant and anti-inflammatory properties and reducing proliferation in orbital fibroblasts [ 70 – 72 ]. In addition to the above effects, Ursolic acid [ 57 – 59 ] and Rutin [ 73 , 74 ] are reported to promote apoptosis and regulate immune in other cell systems and animal models. Eight important therapeutic targets with the degree > 7.83 are PTGS2, MAPK3, AKT1, TNF, MAPK1, CASP3, IL6 and MMP9.…”

Targeting Multiple Signaling Pathways in Cancer: The Rutin Therapeutic Approach

“…A combination of 5-fluorouracil (5-FU) and rutin synergistically acts as a potential cytotoxic agent against PC3 prostate cancer cells. Furthermore, combined treatment hampers cell proliferation, augments apoptosis, downregulates Bcl-2 signaling protein, and upregulates p53 expression [ 28 ]. Overactivation of Bcl-2 proto-oncogene plays a critical role in abrogating cell apoptosis and tumor suppressor protein p53 activity [ 61 ].…”

“…Rutin has also been called vitamin P, as it is widely distributed in various plants, from vegetables and fruits to medicinal plants, including asparagus, buckwheat, apricots, apples, cherries, grapes, grapefruit, plums, oranges, and tea. Rutin has shown ubiquitous pharmacological properties, including antioxidant, anti-inflammatory, antiangiogenic, pro-apoptotic, and antiproliferative activities, all of which may participate in the prevention and treatment of cancer [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. Figure 1 displays the chemical structure of rutin and its reversible deglycosylation to produce quercetin.…”