title: Staurosporine-induced apoptosis of HPV positive and negative human cervical cancer cells from different points in the cell cycle.
abstract: 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.
authors.affiliation: Laboratoire de Biologie cellulaire et Virale, Faculté de Médecine et de Pharmacie, Place Saint-Jacques, Besançon Cedex, 25030, France.
authors.forename: B
authors.initials: B
authors.lastname: Bernard
authors.forename: T
authors.initials: T
authors.lastname: Fest
authors.forename: J L
authors.initials: JL
authors.lastname: Prétet
authors.forename: C
authors.initials: C
authors.lastname: Mougin
mesh_terms: 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
chemical_list: D019311:Staurosporine