COMPARATIVE ANALYSIS OF THE ANTICANCER ACTIVITY OF ANGIOTENSIN RECEPTOR BLOCKERS - IRBESARTAN AND TELMISARTAN

Objective: Angiotensin receptor blockers (ARBs) are effective hypertensive drugs. Reduction in risk of lung cancer with ARBs was proven in clinical studies. Telmisartan and irbesartan are the second-generation ARBs. This study screens the anticancer activity of these two drugs in a dose-dependent manner using A549 cell line.Methods: Different concentrations of irbesartan and telmisartan were treated on A549 cells and the anticancer activity was evaluated through methylthiazolyldiphenyl-tetrazolium [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity assay. The dot plot of the cytotoxicity results was used to extrapolate the half maximal inhibitory concentration (IC50) values. Microscopic changes in the cells post-treatment with these drugs were also recorded at ideal concentrations.Results: A reduction in cell viability was noted in A549 cells with increasing concentration of the drug. The IC50 values for irbesartan and telmisartan were 31.1 μg and 15.6 μg, respectively. Microscopic observation of the cells shows more rounded and deformed dead cells on telmisartan- and irbesartan-treated cells when compared with the untreated control.Conclusion: The results confirm the anticancer activity of both the drugs with telmisartan being more efficient. The anticancer activity could probably be due to the role of irbesartan and telmisartan in inhibiting mitogen-activated protein kinase cell survival pathway and local angiogenesis

EVALUATION AND COMPARISON OF CYTOTOXIC EFFECT OF VILAZODONE HYDROCHLORIDE WITH 5-FLUOROURACIL IN HT-29 BOWEL CANCER CELL LINE

Objectives: Vilazodone hydrochloride is a novel selective serotonin reuptake inhibitor (SSRI) used to treat major depressive disorders. There are only sparse data available to know about the SSRI’s and its association with colon cancer. This study aims to evaluate and compare the in vitro cytotoxic effect of vilazodone with 5-fluorouracil (5-FU) in HT-29 cell line. Methods: Cell viability was tested by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay (Mosmann, 1983). Test sample and standard drug in variable concentrations were added to the HT-29 cell lines for incubation over 24 h under ideal conditions. After washing the test and standard drug sample from the well with saline, MTT was added and incubated for 4 h. Dimethyl sulfoxide of 1 ml was added in all wells after incubation with MTT. The absorbance at 570 nm was measured with an ultraviolet - spectrophotometer. Results: The values were tabulated, and the graph was plotted to find the IC-50 value (inhibitory concentration at 50%) which was struck at 28.5 μg/ml and12. 8 μg/ml for vilazodone hydrochloride and 5-FU, respectively. Conclusion: The results show that vilazodone hydrochloride has good anticancer property comparable with 5-FU, which would probably play a role as a cytotoxic agent in tumor cells. The proposed mechanism of action could be by activation of caspase-3 enzyme, thereby increasing apoptosis and indicates its use in coexisting depression and colon carcinoma. Other mechanism includes suppression of oncogene p53, which can be confirmed by future studies