RNA and proteins extracted from the regenerating tail of lizards determine inhibition of cancer cell proliferation in vitro

Recent studies suggest that tail regeneration in lizards begins with a tumor-like stage usually termed regenerative blastema. Oncogenes and tumor suppressors are activated in blastema cells, resulting in a balanced cell proliferation that does not turn the blastema into a tumor. This outgrowth elongates forming new tissues and tail. We previously showed that physiological extracts from regenerating lizard tissues inhibit the growth of cancer cells <i>in vitro</i> within 2-4 days of administration, demonstrating that the growing lizard blastema contains regulatory molecules which can also influence human cancer cells. The molecules responsible for this inhibition were not identified in that initial study. In the present experimental study, after specific extractions of RNAs and/or proteins from the regenerating tail of lizard, we have confirmed the inhibition of breast cancer cell vitality <i>in vitro</i> within 2-3 days from their addition to the culture medium. Proteolysis or heat denaturation of proteins abolished the inhibitory effect. RNA delivered to breast cancer cells <i>in vitro</i> through lipid vesicles (liposomes) showed the highest inhibition of cancer cells vitality. Cell degeneration, detected by microscopy, revealed that RNA is more effective than proteins extracted from regenerating tissues. The present observations further suggest that RNAs coding for known tumor suppressor proteins, and non-coding RNAs that are highly expressed in the regenerating tail, may be key inhibitors (tumor suppressors) of blastema and cancer cell proliferation. The evolution of a mechanism for the self-remission of tumor growth in lizards remains uncertain, but continuing study of this reptile may help uncover natural mechanisms for tumor growth inhibition.