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

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 mu M 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. Keywords Author Keywords:Apoptosis; Rutin; 5-Fluorouracil; Prostate cancer KeyWords Plus:PROSTATE-CANCER; COMBINATION THERAPY; NATURAL-PRODUCTS; 5-FU; DEATH; CHEMOTHERAPY; EFFICACY; CURCUMIN; DAMAG

Bromelain-based chemo-herbal combination effect on human cancer cells: in-vitro study on AGS and MCF7 proliferation and apoptosis

Aim. Chemo-herbal combinations promise new clinical anticancer therapeutic modalities. The current study investigated and compared the in vitro effects of a bromelain-based chemo-herbal combination to/with cisplatin or 5-FU, with regard to the proliferation and apoptosis of human gastric AGS and breast MCF7 cell lines. Material and methods. AGS and MCF7 cells were either treated with different concentrations of bromelain, cisplatin or 5-FU; or with bromelain-cisplatin and bromelain-5-FU combinations for 48h. Cell proliferative inhibition and inductive apoptosis were appraised using MTT assay and flowcytometry, respectively. Kruskal-Wallis and Dunn's tests were used to analyze differences in cell groups' means. Results. AGS proliferation was adversely affected by single treatments of bromelain and cisplatin (p<0.003) or 5-FU (p<0.05). The anti-proliferative impact of single treatments was more pronounced on MCF7 cells. The bromelain-cisplatin combinations displayed synergistic effect on MCF7 cells (CIs <= 1), while being additive or antagonistic with cisplatin IC30 and IC40 to AGS cell proliferation, respectively. In addition, bromelian-5-FU combinations showed synergistic effect on AGS cells, while antagonistic to MCF7 cells. In terms of cell apoptosis induction, bromelain (IC30)-cisplatin (IC20) displayed additive effect on MCF7, compared to cisplatin single treatment (p<0.04), while bromelain (IC40)-5-FU (IC10) and bromelain (IC30)-5-FU (IC20) afforded additive apoptotic effects on AGS (p<0.04) and MCF7 (p<0.05), respectively, in comparison to 5-FU single treatment. Conclusion. A bromelain-based combination using cisplatin showed concordant effects on cell proliferation impediment and apoptotic induction on MCF7, while the same results were noticed with a bromelain-5-FU combination to AGS cells. The bromelain-based chemo-herbal pathways should further be investigated in the frame of multi-chemotherapeutic drugs researches. Keywords:AGS cells; Bromelain; Cisplatin; 5-FU; MCF7 cell

Bromelain-based chemo-herbal combination effect on human cancer cells: in-vitro study on AGS and MCF7 proliferation and apoptosis

Aim. Chemo-herbal combinations promise new clinical anticancer therapeutic modalities. The current study investigated and compared the in vitro effects of a bromelain-based chemo-herbal combination to/with cisplatin or 5-FU, with regard to the proliferation and apoptosis of human gastric AGS and breast MCF7 cell lines

Chemopreventive effect of spirulina microalgae on an animal model of glioblastoma via down‐regulation of PI3K / AKT / mTOR and up‐regulation of miR ‐34a/ miR‐125B expression

Recent studies suggest that Spirulina may have great therapeutic benefits due to its antioxidant and anti-inflammatory properties. The primary objective of this study was to evaluate the chemopreventive properties of the Spirulina microalgae (Spi) on the regression and survival of tumor, histopathological features of glioblastoma, and detection of the molecular mechanism of Spi. Tumor viability versus Spi was determined using the MTT assay. In vivo antitumor activity of Spi was studied using the glioblastoma model. After tumor induction, the animals were euthanized, and their brains were removed. Histological evaluation was performed for tumor size and manifestation. The mechanisms of the anticancer effects of Spi were investigated by evaluating the microRNAs and their targets. The results demonstrated that Spi inhibited C6 and U87 cell proliferation and induced cell death. Histopathologic results showed that the administration of Spi could delay the development of tumors and prolonged the survival of tumor-bearing animals. Furthermore, Spi significantly upregulated miR-34a and miR-125b that have a key role in the progression of PI3K/AKT/mTOR pathway. This is the first in vivo report on the chemo-preventive effect of Spi against glioblastoma, suggesting its potential use in the chemoprevention of this cancer and the antiglioma molecular mechanism of S