Anti-cell Proliferative Mechanism of Doxazosin on Human Oral Cancer Cells Through the Modulation of Antioxidant and Apoptotic Pathway.

Abstract

Oral squamous cell carcinoma (OSCC), a global threatening disease, is reported mostly in the middle and elderly male population. Even though the exact cause of OSCC was not known, consumption of tobacco in any form has been reported in most of OSCC patients. OSCC is a massive invasive type of cancer which easily spreads to the distant organs. Hence treating it at appropriate time is necessary and the rate of OSCC incidence is also constantly increasing. At present, chemoradiation is the only therapy prescribed for OSCC patients which renders various side effects. Hence, the treatment with lesser side effect was of current research interest. Doxazosin (α1 adrenorecptor antagonist) had been proven to render anticancer effect in prostate, renal, hepatic, and ovarian cancers but its role in oral cancer cells was not been elucidated. Therefore, we have assessed the anticancer effect of doxazosin on oral squamous cancer cells via through the induction of apoptosis, and antioxidant property. The cytoprotective effect of doxazosin on normal Vero cells and anticancer effect on oral cancer KB cells were analyzed with MTT assay. Doxazosin antioxidant activity were analyzed by their reactivity with free radicals and metal ions by the method of FRAP, DPPH, chemilumiscence, and ORAC assay. The antioxidant levels were also assessed by TBARS, SOD, and glutathione levels, and later on apoptosis staining techniques like DCFH-DA, Rhodamine 123, and AO/EtBr stain were conducted. Apoptosis was confirmed by estimating the levels of apoptotic proteins in doxazosin-treated KB human oral cancer cells by ELISA method. The results from our study show that doxazosin is a potent antioxidant and it significantly induces apoptosis in human oral cancer by altering various cellular molecules at downstream signaling which has been depict in the results. Our study proves doxazosin as a potent anticancer drug which may be used in the treatment of oral carcinoma, if it is subjected to further research using human clinical trials.