Neocarzinostatin induces an effective p53-dependent response in human papillomavirus-positive cervical cancer cells

Adriana Bañuelos, Elba Reyes, Rodolfo Ocadiz, Elizabeth Alvarez, Martha Moreno, Alberto Monroy, Patricio Gariglio

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

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.
Original languageAmerican English
Pages (from-to)671-680
Number of pages602
JournalJournal of Pharmacology and Experimental Therapeutics
DOIs
StatePublished - 1 Aug 2003

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Zinostatin
Uterine Cervical Neoplasms
cancer
apoptosis
Oncogene Proteins
Cell Proliferation
Apoptosis
proteins
G2 Phase Cell Cycle Checkpoints
Tumor Suppressor Protein p53
tumor suppressor proteins
Proteins
Double-Stranded DNA Breaks
deoxyribonucleic acid
Proteasome Endopeptidase Complex
Ubiquitin
Biological Products
DNA Damage
genome
Carcinogenesis

Cite this

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abstract = "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.",
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Neocarzinostatin induces an effective p53-dependent response in human papillomavirus-positive cervical cancer cells. / Bañuelos, Adriana; Reyes, Elba; Ocadiz, Rodolfo; Alvarez, Elizabeth; Moreno, Martha; Monroy, Alberto; Gariglio, Patricio.

In: Journal of Pharmacology and Experimental Therapeutics, 01.08.2003, p. 671-680.

Research output: Contribution to journalArticleResearchpeer-review

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