Human papillomaviruses type 16+ and 18+ cervical carcinoma cells are sensitive to staurosporine-mediated apoptosis.
We have recently shown that staurosporine (ST) can trigger apoptosis of CaSki and HeLa cervical tumor cells from G2/M checkpoint, though the mechanism remains elusive. In this study, we reported that ST induced the inhibition of E6 and E7 viral oncogene and MDM2 expression, while it led to increased levels of p53, which was transiently located to mitochondria. Additionally, the proteins of the p53-regulated genes, p21(WAF1) and Bax, were increased with a similar time, while Bcl-2 and Bcl-X(L) expression was lowered. Upon ST treatment, the cytochrome c was released into the cytosol and, then, activation of caspases-9 and -3 led to Poly(ADP)RibosePolymerase (PARP) cleavage. Finally, characteristic morphological signs confirmed the apoptosis execution. Thus, taken together, all these observations suggest that apoptosis can be reactivated in HPV-positive human carcinoma cells and highlight that ST could be used as a potently chemotherapy agent to enhance the sensitivity of tumor cells to apoptosis.
Bernard
Benjamin
B
Equipe d'Accueil EA 3181, Institut d'Etude et de Transfert de Gènes (IETG), Laboratoire de Biologie Cellulaire et Moléculaire, CHU Jean-Minjoz, Boulevard Fleming, 25030 Besançon cedex, France.
Prétet
Jean-Luc
JL
Charlot
Jean-François
JF
Mougin
Christiane
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D016158:Genes, p53 / Q000187:drug effects / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral / Q000187:drug effects / Q000378:metabolism; D027383:Papillomaviridae / Q000187:drug effects; D030361:Papillomavirus Infections / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019311:Staurosporine / Q000494:pharmacology*; D014412:Tumor Virus Infections / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000821:virology*
D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052633:E7 protein, Human papillomavirus type 18; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D019311:Staurosporine