Insights into mechanism of tumour promotion by mezerein.

ABSTRACT

The objective of this study was to gather insights and compare the mode of action of the non phorbol, diterpene mezerein with the phorbol ester, phorbol-12-myristate-13 acetate, in normal and transformed cells. Both phorbol-12-myristate-13 acetate and mezerein are shown to activate the signal transduction pathways involving post translational modification of proteins by poly ADP-ribosylation and by protein kinase C, but to varying extents and showed different time kinetics and cell type differences.Multiple nuclear proteins, especially histones H3d, A24 and HI served as acceptors of poly ADP-ribose in response to PMA in both NIH 3T3 and HDCS cells whereas H1 and H2B were the major acceptors in case of mezerein treatment, similarly in both NIH 3T3 and HDCS cells. The results suggest an epigenetic mechanism (s) in tumour promotion by mezerein.