Abstract
DNA damaging chemotherapeutic agents like carboplatin (Carb) and 5-fluorouracil (5-FU), whose effects are mediated through diverse intracellular targets, induce apoptosis in various cancer cells including human papillomavirus (HPV) positive HEp-2 and KB cells. The present work reports the involvement of Bcl-2 in response to the exposure of HEp-2 and KB cells to Carb or 5-FU. We demonstrate that both these drugs are potent inducers of apoptosis. Apoptosis was preceded by decrease in Bcl-2 protein level accompanied by caspase-9 activation and poly(ADP-ribose) polymerase (PARP) cleavage without altering Bax expression. Further analysis revealed down-regulation of Bcl-2 mRNA as well as protein in drugs treated cells. Ectopic expression of Bcl-2 protected cells against drugs mediated DNA damage-induced apoptosis. Overall, data indicates that genotoxic stress leads to down-regulation of Bcl-2 in HEp-2 and KB cells, which plays a decisive role in the outcome of stress in these cells.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimetabolites, Antineoplastic / pharmacology*
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Antineoplastic Agents / pharmacology*
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Apoptosis*
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Carboplatin / pharmacology*
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Caspase 9
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Caspases / metabolism*
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Cell Line, Tumor / drug effects
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Down-Regulation
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Enzyme Activation / drug effects
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Fluorouracil / pharmacology*
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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KB Cells
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Papillomaviridae*
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Papillomavirus Infections / drug therapy*
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Poly(ADP-ribose) Polymerase Inhibitors
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Poly(ADP-ribose) Polymerases / metabolism
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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RNA, Messenger / metabolism
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Transfection
Substances
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Antimetabolites, Antineoplastic
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Antineoplastic Agents
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Poly(ADP-ribose) Polymerase Inhibitors
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Carboplatin
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Poly(ADP-ribose) Polymerases
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CASP9 protein, human
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Caspase 9
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Caspases
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Fluorouracil