Syracuse

Human papillomaviruses type 16+ and 18+ cervical carcinoma cells are sensitive to staurosporine‐mediated apoptosis

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Bernard, Benjamin | Prétet, Jean‐luc | Charlot, Jean‐françois | Mougin, Christiane

Edité par CCSD ; Wiley -

International audience. Abstract 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.

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