Staurosporine-induced apoptosis of HPV positive and negative human cervical cancer cells from different points in the cell cycle.
In the present study, we compare the sensitivity of CaSki and HeLa cells (HPV positive, wild-type p53) and C33A cells (HPV negative, mutated p53) to a protein kinase inhibitor, the staurosporine (ST). We show that ST can reversibly arrest the three cervical-derived cell lines, either in G1 or in G2/M. Beyond certain ST concentrations or/and over 24 h exposure, the cells underwent apoptosis. This process took place in G1 and G2/M for C33A and CaSki plus HeLa cell lines, respectively. By using an in vitro cell-free system, we demonstrated that cytoplasmic extracts from apoptotic cells were sufficient to induce hallmarks of programmed cell death on isolated nuclei. Moreover, we found that only G2/M cytoplasmic extracts from viable CaSki and HeLa cells supplemented with ST, triggered apoptosis while exclusively G1 cytoplasmic fractions from C33A cells were efficient. Our study describes a possible involvement of the HPV infection or/and p53 status in this different ST-induced apoptosis susceptibility.
Bernard
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B
Laboratoire de Biologie cellulaire et Virale, Faculté de Médecine et de Pharmacie, Place Saint-Jacques, Besançon Cedex, 25030, France.
Fest
T
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Prétet
J L
JL
Mougin
C
C
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006367:HeLa Cells; D052161:Human papillomavirus 18; D006801:Humans; D020287:In Situ Nick-End Labeling; D030361:Papillomavirus Infections / Q000473:pathology*; D019311:Staurosporine / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology
D019311:Staurosporine