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.
Singh
Mayank
M
Department of Biochemistry, All India Institute of Medical Science, Room no 3027A, Ansari Nagar, New Delhi 110029, India.
Singh
Neeta
N
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology* / Q000821:virology*; D051028:bcl-2-Associated X Protein / Q000235:genetics; D051020:bcl-X Protein / Q000235:genetics
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)