Inhibition of B16 Mouse Melanoma Cell Growth and Induction of Apoptotic Cell Death with 8-Chloroadenosine-3',5'-monophosphate and Tiazofurin

doi:10.1196/annals.1329.048

Novel antineoplastic agents, 8-chloroadenosine 3',5'-monophosphate(8-Cl-cAMP) and tiazofurin (TR), have been shown to be effectiveagainst different malignant cells. Through specific mechanismsof action they modulate the cellular signal transduction pathway,thereby causing growth inhibition, cell differentiation, andapoptosis. The aim of this work was the in vitro study of either8-Cl-cAMP or TR effects on B16/F10 and B16/C3 mouse melanomacell growth and cell death. Significant cell growth inhibitionwas obtained after the application of 8-Cl-cAMP or TR. The presenceand number of apoptotic cells was evaluated using agarose gelelectrophoresis and flow cytometry. The number of apoptoticnuclei, after treatment with antineoplastic agents, did notsignificantly change in B16/F10 cells, although it did showa significant increase in B16/C3 cells. The expression of c-mycdid not significantly change in B16/F10 cells after treatmentwith 8-Cl-cAMP or TR. The same results were obtained in B16/C3cells after treatment with 8-Cl-cAMP. The level of c-myc expressionshowed a significant increase in B16/C3 cells after treatmentwith TR. Concerning the effects that the analyzed agents exhibitedon melanoma cells and other cancer cells, further preclinicalstudies of these drugs will potentially lead to better understandingof the molecular mechanisms of their action and finally moreefficient therapeutic approaches to malignant diseases.