Induction of apoptosis by hydrogen peroxide in HPV 16 positive human cervical cancer cells: involvement of mitochondrial pathway

Cervical cancer is the second most common malignant neoplasm in women, in terms of incidence and mortality rates worldwide, and is associated with excessive inflammation. This involves the expression of both pro- and anti-apoptotic proteins that have varied effect on tumor growth and metastasis. The objective of the present study was to elucidate the effect of hydrogen peroxide (H2O2) on apoptotic signal molecules in vitro in SiHa and CaSki cell lines expressing the human papilloma virus 16 E6 protein, which causes the ubiquitin-mediated degradation of p53 protein and is thus p53 deficient. The p53 is known to act as a cellular stress sensor and triggers apoptosis. We demonstrate, here, that in HPV 16 positive cell lines apoptosis is triggered by upregulation of p73, which causes activation of pro-apoptotic Bax accompanied by down regulation of anti-apoptotic Bcl xl, release of cytochrome c from mitochondria and activation of caspases-9 and -3.