Hydrogen peroxide induces apoptosis in HeLa cells through mitochondrial pathway.
Cervical cancer is the most common cancer amongst females in India and is associated with high risk HPVs, reactive oxygen species (ROS), and excessive inflammation in most cases. ROS in turn affects the expression of pro- and anti-apoptotic proteins. The objective of the present study was to elucidate the effect of hydrogen peroxide (H(2)O(2)) on apoptotic signaling molecules in vitro. HeLa cell line expresses the Human papilloma virus - 18, E6 oncoprotein which causes the ubiquitin mediated degradation of p53 protein and is thus p53 deficient. p53 is known to act as a cellular stress sensor and triggers apoptosis. p73, a member of the p53 family also induces apoptosis in response to DNA damaging agents but unlike p53, it is infrequently mutated in human tumors. We demonstrate here, that in HeLa cells, apoptosis is triggered by H(2)O(2) via the mitochondrial pathway involving upregulation of p73, and its downstream target Bax. This was accompanied by upregulation of ERK, JNK, c-Myc, Hsp-70 and 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, New Delhi 110029, India.
Sharma
Himani
H
Singh
Neeta
N
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000502:physiology; D053453:Caspase 9 / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006367:HeLa Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis; D051020:bcl-X Protein / Q000378:metabolism
C494811:BCL2L1 protein, human; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4; D053148:Caspase 3; D053453:Caspase 9; D016283:Proto-Oncogene Proteins p21(ras)