PT - JOURNAL ARTICLE AU - Adriana BaƱuelos AU - Elba Reyes AU - Rodolfo Ocadiz AU - Elizabeth Alvarez AU - Martha Moreno AU - Alberto Monroy AU - Patricio Gariglio TI - Neocarzinostatin Induces an Effective p53-Dependent Response in Human Papillomavirus-Positive Cervical Cancer Cells AID - 10.1124/jpet.103.051557 DP - 2003 Aug 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 671--680 VI - 306 IP - 2 4099 - http://jpet.aspetjournals.org/content/306/2/671.short 4100 - http://jpet.aspetjournals.org/content/306/2/671.full SO - J Pharmacol Exp Ther2003 Aug 01; 306 AB - Human papillomavirus (HPV) E6 viral oncoprotein plays an important role during cervical carcinogenesis. This oncoprotein binds the tumor suppressor protein p53, leading to its degradation via the ubiquitin-proteasome pathway. Therefore, it is generally assumed that in HPV-positive cancer cells p53 function is completely abolished. Nevertheless, recent findings suggest that p53 activity can be recovered in cells expressing endogenous E6 protein. To investigate whether p53-dependent functions controlling genome integrity, cell proliferation, and apoptosis can be reactivated in cervical cancer cells, we examined the capacity of HeLa, INBL, CaSki, C33A, and ViBo cell lines to respond to neocarzinostatin (NCS), a natural product which induces single- and double-strand breaks in DNA. We found that NCS treatment inhibits cellular proliferation through G2 cell cycle arrest and apoptosis induction. This effect was preceded by nuclear accumulation of p53 protein and by an increase of p21 transcripts. Although apoptosis was blocked in ViBo cells (HPV-negative), nuclear accumulation of transcriptionally active p53 and inhibition of cell proliferation are observed after NCS treatment. These results suggest that HPV-positive cervical cancer cells are capable of responding efficiently to DNA damage provoked by NCS treatment through a p53-dependent pathway in spite of the presence of E6 protein. The American Society for Pharmacology and Experimental Therapeutics