Idaein chloride induced p53 dependent apoptosis in cervical cancer cells through inhibition of viral oncoproteins

Host dependent expression of early HPV oncoproteins, E6 and E7 play central role in the formation of cervical carcinoma. Presently, we have shown that the cyanidin analog, idaein chloride treatment induced dose dependent apoptosis (IC50 = 2.579 μg/ml) in HPV positive - HeLa cells. Flow cytometric analysis showed arrest of cell cycle at G1 phase with an increased sub G1 cell population on 12th h of exposure. The recorded reduced expression levels of cell cycle proteins - cyclin D, cdk 4 and cdk 6 confirmed the occurrence of cell cycle arrest at G1 phase. In addition, the idaein chloride significantly inhibited the expression of E6 and E7 proteins, resulting in p53 re-expression and hence triggering of p53 dependent apoptosis. This has been further supported by the recorded variations in the expression patterns of p21/WAF, pRb and E2F regulatory proteins. In case of mitochondrial apoptotic markers, the expression of Bax was restored and Bcl-2 level got decreased at 12th h. Cleaved caspases 3 & 9 and PARP were also observed after 3 h of treatment. Interestingly, the epigenetic regulatory enzymes (DNMTs) were inhibited by idaein chloride. Thus, idaein chloride could be a potent source for developing a drug against cervical carcinoma.