Pharmacological and Molecular Modeling Studies on the Effect of Biochanin-A in Colon Cancer Cells

Abstract

Colorectal carcinoma is the third most commonly diagnosed type of cancer and also is the third most leading cause of cancer-related death worldwide. 5-fluorouracil is the first-line therapy for colorectal cancer patients. Current treatment protocols consider the evaluation of 5-FU in combination with other anticancer chemotherapies to enhance its efficacy and tolerability. Isoflavones are naturally occurring bio-active compounds that exhibit anti-oxidant and anti-cancer properties. Its anticancer effect occurs through inhibition of protein tyrosine kinases, induction of apoptosis and antiangiogenenic effects. Biochanin-A (Bio-A) is one of the isoflavones that possesses promising anticancer effects against wide range of cancers including prostate, breast and oral cancer. This study aimed to investigate the potential modulatory effects of Bio-A on 5-FU cytotoxicity in colon cancer cells both in vitro and to verify the effectiveness of the combination in vivo in Ehrlich solid phase carcinoma model. The main findings of the current study can be summarized as follows: 1. Bio-A synergistically enhanced 5-FU cytotoxicity in vitro in colon cancer cell lines Caco2 and HCT116 and the effect was verified in vivo in Ehrlich solid phase carcinoma model. 2. Bio-A significantly suppressed Akt-phosphorylation. 3. Bio-A boosted the ratio of phosphorylated β-catenin(p-S45)/total β-catenin. 4. Cell-cycle regulatory protein, cyclin D1, decreased significantly in tumor specimens of 5-FU/Bio-A-treated mice. 5. 5-FU/Bio-A combination led to significant downregulation of the level of invasion and migration marker metalloproteinase-2 (MMP2)