Effects of polyamines, polyamine synthesis inhibitors, and polyamine analogs on casein kinase II using Myc...

Polyamines, casein kinase II (CKII), and the myc oncogene are directly involved in the regulation of molecular events in cell proliferation, differentiation, and apoptosis. Each is increased in rapidly growing cancer cells. In our current study, we showed that the Km values for purified CKII were similar for casein and Myc oncoprotein under a variety of assay conditions, and that specific natural and synthetic polyamines stimulated CKII phosphorylation of Myc oncoprotein 2- to 20-fold via increases in Vmax. When polyamine synthesis inhibitors and analogs were studied with this purified enzyme system, two polyamine analogs (N1,N12-bis-(ethyl)-spermine [BESpm] and 1,19-bis-(ethylamino)-5,10,15, triazononadecane [BE4X4]), which did not affect basal enzyme activity, did prevent (or inhibit) polyamine-stimulated CKII activity by approximately 70 and 85 percent, respectively. Because the Myc oncoprotein transactivates several genes for key proteins involved in the regulation of cellular proliferation, including the omithine decarboxylase gene (rate-limiting enzyme of polyamine synthesis), we suggest that there may be linkages between polyamines, CKII, and Myc in the control of cellular proliferation. We also suggest that the anticancer drugs BESpm and BE4X4 may inhibit cancer cell proliferation partially through interference with the above-suggested CKII linkages.