THE ANTIPROLIFERATIVE RIMINOPHENAZINE AGENTS CLOFAZIMINE AND B669 PROMOTE LYSOPHOSPHOLIPID-MEDIATED INHIBITION OF NA-ADENOSINE TRIPHOSPHATASE-ACTIVITY IN CANCER CELL-LINES IN-VITRO(, K+)

The effects of the anti-proliferative, phospholipase A(2) (PLA(2))-act ivating riminophenazine agents, clofazimine and B669, on the Na+, K+-a denosine triphosphatase activity of the FaDu human pharynx squamous ca rcinoma cell line have been investigated in vitro. At concentrations o f 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-neutral izing agents alpha-tocopherol and lysophospholipase. Riminophenazine-m ediated inhibition of Na+, K+-ATPase activity was also observed with t he HeLa (human cervix epitheloid carcinoma) and T24 (human transitiona l cell bladder carcinoma) cell lines. The anti-proliferative activity of clofazimine and B669 is therefore probably achieved by lysophosphol ipid-mediated inactivation of Na+, K+-ATPase.