EFFECTS OF DOLASTATINS ON HUMAN B-LYMPHOCYTIC LEUKEMIA-CELL LINES

Dolastatins are naturally occurring peptides isolated from marine animals and are known to be potent anti-neoplastic agents. Here, the three compounds dolastatin 10 (Dola 10), dolastatin 15 (Dola 15) and deo-dolastatin 10 (Deo-Dola 10) were added to cultures of two human chronic B-leukemia cell lines, JVM-2 and EHEB. The three dolastatins (Dola 10 > Dola 15 > Deo-Dola 10) inhibited cell proliferation and immunoglobulin production. Decreased cell growth and lack of accumulation of immunoglobulin was not caused by cytotoxicity as cell viability in the cultures remained high. The unchanged surface marker immunoprofiles during treatment and a predominance of treated cells in S and G2/M phase suggested cytostatic rather than directly cytotoxic effects. Exposure to these reagents increased quickly, albeit only short c-myc and bcl-2 mRNA expression. These results indicate that the three dolastatins are potent inhibitors of leukemic B-cell proliferation.