Synergistic inhibition of growth and induction of apoptosis by 8- chloro-cAMP and paclitaxel or cisplatin in human cancer cells

Giampaolo Tortora, Giuditta Di Isernia, Claudia Sandomenico, Roberto Bianco, Grazia Pomatico, Stefano Pepe, A. Raffaele Bianco, Fortunato Ciardiello

Research output: Contribution to journalArticlepeer-review

Abstract

8-Chloro-cAMP (8-Cl-cAMP) is 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.

Original languageEnglish
Pages (from-to)5107-5111
Number of pages5
JournalCancer Research
Volume57
Issue number22
Publication statusPublished - Nov 15 1997

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Synergistic inhibition of growth and induction of apoptosis by 8- chloro-cAMP and paclitaxel or cisplatin in human cancer cells'. Together they form a unique fingerprint.

Cite this