Bacterial proteins as potential drugs in the treatment of leukemia.

ABSTRACT

Azurin and Laz are bacterial proteins that have been shown to exert anticancer effects against a variety of solid tumors. Their effects on liquid cancers have never been studied. We now show that they are also effective against liquid-borne cancers such as leukemia. Azurin and Laz can each enter in two leukemia cell lines but Laz exerts a greater cytotoxic effect on both K562 and HL60 cells, while having little effect on peripheral blood mononuclear cells, where they have very limited entry. In addition to Azurin and Laz, we have recently identified another protein, Pa-CARD, from Pseudomonas aeruginosa that carries a caspase recruitment domain (CARD)-like domain. This CARD domain polypeptide, called Pa-CARD, demonstrates cytotoxic activity against leukemia cells. In the leukemia cell lines, HL60 and K562, the anticancer activity of Laz and Pa-CARD is mediated through cell cycle arrest at the G2/M phase involving the Wee1 protein stabilization and the depletion of phosphorylated AKT-Ser-473, the active form of a serine/threonine kinase that is often dysregulated in many cancer types.