Chiral β‐arylchalcogenium azide induce apoptosis and regulate Oxidative Damage on Human Bladder Cancer Cells

Abstract

AbstractIn the present study, we aimed to evaluate the cytotoxic effect of chiral β‐Aryl‐chalcogenium azide compounds in vitro against the human bladder cancer cell line 5637. The cell growth inhibition was evaluated by MTT assay. The apoptosis induction and cellular viability were measured by DAPI staining and live/dead assay, respectively. Also, gene expression of pro‐apoptotic, anti‐apoptotic and oxidative stress pathways were investigated by qRT‐PCR. Finally, in silico molecular docking between the compounds and proteins involved in apoptotic and cell growth pathways was performed as well. Our results showed that 5c [(S)‐(2‐azido‐1‐phenyl‐3‐telurophenyl)‐propane)] and 5j [(S)‐(2‐azido‐1‐phenyl‐3‐teluro‐p‐methoxy‐phenyl)‐propane)] compounds presented concentration‐dependent cytotoxicity. Apoptosis analysis showed chromatin condensation in 13 % and 20.3 % of cells treated with compounds 5 c and 5 j, respectively, compared to untreated cells (2.34 %). Moreover, 5 c increased the relative expression of p53, Caspase‐3, Caspase‐9, SOD and CAT genes. Meanwhile, 5 j increased the expression of p53, p21, Caspase‐3, Caspase‐9, Bax, SOD, CAT, GPx, GR and iNOS genes. Finally, molecular docking showed that 5 c has a binding affinity to Survivin, Bcl‐XL, RSK2, SGK1, while 5 j showed binding affinity to the SGK1 protein only. These findings suggest that β‐Aryl‐chalcogenium azide compounds could have a potential antitumoral effect in bladder cancer cells in vitro.