8-Chloro-cAMP enhances the growth inhibitory effect of cytotoxic drugs in human colon cancer cells

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

Research output: Contribution to journalArticle

Abstract

8-Cl-cAMP is a novel agent able to inhibit the growth of a wide variety of cancer cell types in vitro and in vivo by interfering with the protein kinase A type I (PKAI), a protein directly involved in mitogenic signalling and neoplastic transformation. In a recent phase I study conducted in cancer patients we have demonstrated that 8-Cl-cAMP, at doses devoid of toxicity, may achieve plasma concentrations in a range previously shown effective for cancer cell growth inhibition. In the present study we have investigated the effect of 8-Cl-cAMP in association with cytotoxic drugs acting by erent mechanisms of action on the growth of LS174T and GEO human colon cancer cells. We here demonstrate that 8-Cl-cAMP administered after the cytotoxic drugs does not interfere with their growth inhibitory effect but rather is additive with most of them. Moreover, a synergistic effect was observed when 8-Cl-cAMP was administered after cisplatin or paclitaxel. The sequence of treatment seems to be important since pretreatment with 8-Cl-cAMP interferes with the effect of the cytoxic drugs. These results demonstrate that 8-Cl-cAMP is not only able to induce cell growth inhibition when used alone but also exhibit the capacity to enhance the efficacy of different cytotoxic drugs.

Original languageEnglish
Pages (from-to)1233-1237
Number of pages5
JournalInternational Journal of Oncology
Volume9
Issue number6
Publication statusPublished - Dec 1996

Keywords

  • 8-chloro-cAMP
  • cisplatin
  • colon cancer
  • paclitaxel

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Di Isernia, G., Ciardiello, F., Sandomenico, C., Pepe, S., Bianco, A. R., & Tortora, G. (1996). 8-Chloro-cAMP enhances the growth inhibitory effect of cytotoxic drugs in human colon cancer cells. International Journal of Oncology, 9(6), 1233-1237.