Inhibition of B16 mouse melanoma cell growth and induction of apoptotic cell death with 8-chloroadenosine-3',5'-monophosphate and tiazofurin.

Novel antineoplastic agents, 8-chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) and tiazofurin (TR), have been shown to be effective against different malignant cells. Through specific mechanisms of action they modulate the cellular signal transduction pathway, thereby causing growth inhibition, cell differentiation, and apoptosis. The aim of this work was the in vitro study of either 8-Cl-cAMP or TR effects on B16/F10 and B16/C3 mouse melanoma cell growth and cell death. Significant cell growth inhibition was obtained after the application of 8-Cl-cAMP or TR. The presence and number of apoptotic cells was evaluated using agarose gel electrophoresis and flow cytometry. The number of apoptotic nuclei, after treatment with antineoplastic agents, did not significantly change in B16/F10 cells, although it did show a significant increase in B16/C3 cells. The expression of c-myc did not significantly change in B16/F10 cells after treatment with 8-Cl-cAMP or TR. The same results were obtained in B16/C3 cells after treatment with 8-Cl-cAMP. The level of c-myc expression showed a significant increase in B16/C3 cells after treatment with TR. Concerning the effects that the analyzed agents exhibited on melanoma cells and other cancer cells, further preclinical studies of these drugs will potentially lead to better understanding of the molecular mechanisms of their action and finally more efficient therapeutic approaches to malignant diseases.