401. Synergistic inhibition of growth and induction of apoptosis by 8-chloro-cAMP and paclitaxel or cisplatin in human cancer cells
- Author
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Tortora, G., Di Isernia, G., Claudia Sandomenico, Bianco, R., Pomatico, G., Pepe, S., Bianco, A. R., Ciardiello, F., Tortora, G, DI ISERNIA, G, Sandomenico, C, Bianco, R, Pomatico, G, Pepe, S, Bianco, Ar, Ciardiello, Fortunato, Tortora, Giampaolo, Bianco, Roberto, Pepe, Stefano, and Ciardiello, F.
- Subjects
G2 Phase ,Mice, Inbred BALB C ,Paclitaxel ,Transplantation, Heterologous ,apoptosis ,8-Bromo Cyclic Adenosine Monophosphate ,Mice, Nude ,Mitosis ,Antineoplastic Agents ,Drug Synergism ,8-chloro-cAMP ,Mice ,Tumor Cells, Cultured ,Animals ,Humans ,cancer therapy ,Female ,Cisplatin ,Cell Division ,Neoplasm Transplantation ,Tumor Stem Cell Assay - 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.
- Published
- 1997