THE BCL-2 AND P53 ONCOPROTEINS CAN BE MODULATED BY BRYOSTATIN-1 AND DOLASTATINS IN HUMAN DIFFUSE LARGE-CELL LYMPHOMA

The effects of dolastatin 10 (Dol10) and dolastatin 15 (Dol15) alone, and after treatment with bryostatin 1 (Bryo1), on human diffuse large cell lymphoma cell line (WSU-DLCL2) were studied. At a concentration of 1.0 ng/ ml Dol10 and Dol15 showed significant growth inhibition (p < 0.05). This inhibition was intensified when the cells were pretreated for 24 h with 200 nM Bryo1. Bryo1, Dol10 and Dol15 induced apoptosis which was seen on morphological examination, by flow cytometry and DNA fragmentation on agarose gel electrophoresis. Cells pretreated with Bryo1 and then exposed to Dol10 showed an increase in apoptosis compared with cells that were treated with the Dol10, Dol15 alone. Immunocytochemistry revealed that WSU-DLCLS cells express the bcl-2 oncoprotein constitutively. bcl-2 expression was decreased when cells were treated with Bryo1, Dol10 or Dol15 and abolished with the Bryo1/Dol10 combination. WSU-DLCLS cells were negative for p53 protein expression, upon treatment with Bryo1 or Dol10, the expression of p53 was weak and moderate with the Bryo1/Dol10 combination. The inverse correlation between bcl-2 and p53 oncoprotein expression seems to be related to induction of apoptosis in this lymphoma cell line.