GAMMA-LINOLENIC ACID BLOCKS CELL-CYCLE PROGRESSION BY REGULATING PHOSPHORYLATION OF P27(KIP1) AND P57(KIP2) AND THEIR INTERACTIONS WITH OTHER CYCLE REGULATORS IN CANCER-CELLS

gamma-Linolenic acid (gamma-LA), a n-6 essential fatty acid, has been previously shown to affect cell cycle and growth of cancer cells. This study examined the effects of gamma-LA on the cell cycle and cycle re gulators in human colon cancer HT115 and breast cancer MCF7 cells. Bri ef treatment of cancer cells (<2 h) with gamma-LA resulted in a decrea se in the phosphorylation of both cell cycle inhibitors, p27(kip1) and p57(kip2) as shown by immunoprecipitation and Western blotting. Prote in levels of both inhibitors were increased following a prolonged cult ure of cells with the fatty acid. A coprecipitation study showed that in cells treated with gamma-LA there was an increase in the binding of these inhibitors with CDK4, CDC2, and cyclin E. Flow cytometry study indicated an inhibition of cell cycle progression by gamma-LA (G0/G1 - 45.4%, S - 34.6%, G2+M - 20.0% in control, and 70.5%, 21.0%, and 8.5% , respectively, in gamma-LA treated cells). It is concluded that gamma -linolenic acid inhibits cell cycle progression in the cancer cell lin es investigated, via its regulation of the phosphorylation and subsequ ent degradation of p27(kip1) and p57(kip2),nd their interactions with other cycle regulators.