The antiproliferative riminophenazine agents clofazimine and b669 promote lysophospholipid-mediated inhibition of na+, k+-adenosine triphosphatase-activity in cancer cell-lines in-vitro.

The effects of the anti-proliferative, phospholipase A(2) (PLA(2))-activating riminophenazine agents, clofazimine and B669, on the Na+, K+-adenosine triphosphatase activity of the FaDu human pharynx squamous carcinoma cell line have been investigated in vitro. At concentrations of 1.25-10 mu g/ml both agents caused dose-related enhancement of PLA(2), as measured by increased release of lysophosphatidylcholine (LPC), and inhibition of Na+, K+-ATPase in intact cells and isolated membrane preparations. The inhibitory effects of both riminophenazines on the Na+, K+-ATPase activity of FaDu cells were mimicked by reagent LPC and prevented by treatment of the cells with the lysophospholipid-neutralizing agents alpha-tocopherol and lysophospholipase. Riminophenazine-mediated inhibition of Na+, K+-ATPase activity was also observed with the HeLa (human cervix epitheloid carcinoma) and T24 (human transitional cell bladder carcinoma) cell lines. The anti-proliferative activity of clofazimine and B669 is therefore probably achieved by lysophospholipid-mediated inactivation of Na+, K+-ATPase.