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

Dolastatins are naturally occurring peptides isolated from marine anim als and are known to be potent anti-neoplastic agents. Here, the three compounds dolastatin 10 (Dola 10), dolastatin 15 (Dola 15) and deo-do lastatin 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 immunoglobul in production. Decreased cell growth and lack of accumulation of immun oglobulin was not caused by cytotoxicity as cell viability in the cult ures remained high. The unchanged surface marker immunoprofiles during treatment and a predominance of treated cells in S and G2/M phase sug gested cytostatic rather than directly cytotoxic effects. Exposure to these reagents increased quickly, albeit only short c-myc and bcl-2 mR NA expression. These results indicate that the three dolastatins are p otent inhibitors of leukemic B-cell proliferation.