SYNERGISTIC INHIBITION OF GROWTH AND INDUCTION OF APOPTOSIS BY 8-CHLORO-CAMP AND PACLITAXEL OR CISPLATIN IN HUMAN CANCER-CELLS

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 an d, at doses devoid of toxicity, to achieve plasma concentrations in ca ncer 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-inh ibitory effect of paclitaxel or cisplatin in a wide series of cell lin es including human breast, lung, ovary, colon, and head carcinomas and melanoma. A similar effect was also observed with another taxane, doc etaxel, and with the platinum-derivative carboplatin. 8-Cl-cAMP also m arkedly enhanced apoptotic cell death induced by each cytotoxic drug, A cooperative antitumor effect was also observed in vivo, because trea tment with paclitaxel followed by 8-Cl-cAMP markedly inhibited the gro wth of GEO human colon cancer xenografts as compared to paclitaxel alo ne without signs of toxicity. These data demonstrate that 8-Cl-cAMP sy nergistically 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.