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 o f 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 B ryo1 and then exposed to Dol10 showed an increase in apoptosis compare d with cells that were treated with the Dol10, Dol15 alone. Immunocyto chemistry 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 combina tion. WSU-DLCLS cells were negative for p53 protein expression, upon t reatment with Bryo1 or Dol10, the expression of p53 was weak and moder ate 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.