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.