Anti-cancer Potential of Captopril and Botulinum Toxin Type-A and Associated p53 Gene Apototic Stimulating Activity

Abstract

Mutational inactivation of p53 is a key player in the development of human cancer. Thus, retrieving the tumor suppressor activity of p53 gene is considered a novel strategy in cancer therapy. Current study aimed to investigate the anti-cancer potentials of botulinum toxin type-A (BTX-A) and captopril as a trial to shed light on effective anti-cancer therapy with lower side effects. Cytotoxic effect of captopril and BTX-A was determined using MTT assay against colon (HCT116) and prostate cancer (DU145) cells compared to their effect on normal vero cells. Anti-proliferation assay and anti-metastatic effect were carried out using trypan blue exclusion method and wound scratch migration test, respectively. The ability of test drugs to induce apoptosis in cancer cells was examined using real time PCR. Recorded data revealed that captopril exhibited a statistically significant cytotoxicity (P < 0.05) to cancer cells (IC50 values of 1.5 and 1.2 mg/mL) with much lower toxicity to normal cells. At the same time, IC50 values post BTX-A treatment were 7.2 and 6.4 U/mL for HCT116 and DU145 cells, respectively without any toxicity to vero cells. Both drugs showed inhibitory potentials on cellular proliferation and the ability of cancer cells to migrate in scratched monolayers was obviously inhibited along with increasing their concentrations. P53 expression levels in captopril and BTX-A treated DU145 cells were elevated by 4 and 2.5 folds, respectively, while lower level of apoptosis induction in HCT116 cells was observed. Accordingly, BTX-A and captopril could present potential anti-cancer candidates through triggering cancer cells towards self-destruction.