Synergistic inhibition of growth and induction of apoptosis by 8-chloro-cAMP and paclitaxel or cisplatin in human cancer cells.
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| Abstract |
8-Chloro-cAMP (8-Cl-cAMP) is a novel agent that is able to inhibit the growth of a wide variety of cancer cell types in vitro and in vivo and, at doses devoid of toxicity, to achieve plasma concentrations in cancer patients in a range effective for cancer cell growth inhibition. In this study, we have demonstrated that 8-Cl-cAMP, at a dose causing mild or no growth inhibition, synergistically increased the growth-inhibitory effect of paclitaxel or cisplatin in a wide series of cell lines including human breast, lung, ovary, colon, and head carcinomas and melanoma. A similar effect was also observed with another taxane, docetaxel, and with the platinum-derivative carboplatin. 8-Cl-cAMP also markedly enhanced apoptotic cell death induced by each cytotoxic drug. A cooperative antitumor effect was also observed in vivo, because treatment with paclitaxel followed by 8-Cl-cAMP markedly inhibited the growth of GEO human colon cancer xenografts as compared to paclitaxel alone without signs of toxicity. These data demonstrate that 8-Cl-cAMP synergistically increases the antiproliferative activity of taxanes and platinum-derived compounds and provide a rationale to use 8-Cl-cAMP in combination with taxanes and platinum-derived compounds.
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| Authors | G Tortora, G di Isernia, C Sandomenico, R Bianco, G Pomatico, S Pepe, A R Bianco, F Ciardiello |
| Journal | Cancer research (Cancer Res) Vol. 57 Issue 22 Pg. 5107-11 (Nov 15 1997) ISSN: 0008-5472 [Print] United States |
| PMID | 9371510 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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