Protein kinase C isozymes in prostatic epithelial cells from normal, diabetic and insulin-treated diabetic rats

Garcia-Paramio, Pilar; Carmena, Marı́a J.; Guijarro, Luis; Prieto, Juan Carlos

doi:10.1016/0306-3623(95)00035-6

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1998

2003

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Cited by 8 publications

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Topoisomerase I inhibitors and drug resistance

Parchment

Pessina

1998

Multiple Drug Resistance in Cancer 2

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DNA topoisomerase I is a nuclear enzyme which catalyzes the conversion of the DNA topology by introducing single-strand breaks into the DNA molecule. This enzyme represents a novel and distinct molecule target for cancer therapy by antitopoisomerase drugs belonging to the campthotecin series of antineoplastics. As many tumors can acquire resistance to drug treatment and become refractary to the chemotherapy it is very important to investigate the mechanisms involved in such a drug resistance for circumventing the phenomenon.This article describes the role of topoisomerase I in cell functions and the methods used to assess its in vitro catalytic activity. It reviews the mechanisms of cytotoxicity of the most specific antitopoisomerase I drugs by considering also the phenomenon of drug resistance. Some factors useful to drive the future perspectives in the development of new topoisomerase I inhibitors are also evidenced and discussed.

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