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NSAIDs induce apoptosis in nonproliferating ovarian cancer cells and inhibit tumor growth in vivo
Author(s) -
Duncan Kristal,
Uwimpuhwe Henriette,
Czibere Akos,
Sarkar Devanand,
Libermann Towia A.,
Fisher Paul B.,
Zerbini Luiz F.
Publication year - 2012
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1035
Subject(s) - apoptosis , in vivo , pharmacology , sulindac , cell cycle , flufenamic acid , population , cell growth , ovarian cancer , chemistry , cancer cell , cancer research , flurbiprofen , survivin , ibuprofen , cancer , medicine , biology , nonsteroidal , biochemistry , microbiology and biotechnology , environmental health
Ovarian cancer (OC) is one of the most lethal gynaecological cancers, which usually has a poor prognosis due to late diagnosis. A large percentage of the OC cell population is in a nonproliferating and quiescent stage, which poses a barrier to success when using most chemotherapeutic agents. Recent studies have shown that several nonsteroidal anti‐inflammatory drugs (NSAIDs) are effective in the treatment of OC. Furthermore, we have previously described the molecular mechanisms of NSAIDs' induction of cancer apoptosis. In this report, we evaluated various structurally distinct NSAIDs for their efficacies in inducing apoptosis in nonproliferating OC cells. Although several NSAIDs‐induced apoptosis, Flufenamic Acid, Flurbiprofen, Finasteride, Celocoxib, and Ibuprofen were the most potent NSAIDs inducing apoptosis. A combination of these agents resulted in an enhanced effect. Furthermore, we demonstrate that the combination of Flurbiprofen, which targets nonproliferative cells, and Sulindac Sulfide, that affects proliferative cells, strongly reduced tumor growth when compared with a single agent treatment. Our data strongly support the hypothesis that drug treatment regimens that target nonproliferating and proliferating cells may have significant efficacy against OC. These results also provide a rationale for employing compounds or even chemically modified NSAIDs, which selectively and efficiently induce apoptosis in cells during different stages of the cell cycle, to design more potent anticancer drugs. © 2012 IUBMB IUBMB Life, 64(7): 636–643, 2012