title: 8-chloro-cAMP enhances the growth inhibitory effect of cytotoxic drugs in human colon cancer cells.
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 different 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.
authors.affiliation: UNIV NAPLES FEDERICO II,FAC MED & CHIRURG,DIPARTIMENTO & ONCOL MOL & CLIN,CATTEDRA ONCOL MED,I-80131 NAPLES,ITALY.
authors.forename: G
authors.initials: G
authors.lastname: Diisernia
authors.forename: F
authors.initials: F
authors.lastname: Ciardiello
authors.forename: C
authors.initials: C
authors.lastname: Sandomenico
authors.forename: S
authors.initials: S
authors.lastname: Pepe
authors.forename: A
authors.initials: A
authors.lastname: Bianco
authors.forename: G
authors.initials: G
authors.lastname: Tortora