Bryostatin 1 induces apoptosis and augments inhibitory effects of @entity1891 in XXXX @entity4812 .

@entity1 @entity588 @entity5 @entity4812 @entity665 @entity56572 @entity876 @entity13629 @entity1891
Bryostatin 1 (Bryo1), a macrocyclic @entity13629 and a protein kinase C activator, is isolated from the marine bryozoan @entity56572 . In this study we describe its effect, alone or after sequential use with @entity1891 (VCR), on the @entity1 @entity4812 cell line WSU-DLCL2. Our results show that both Bryo1 and VCR induced apoptosis as demonstrated by morphological examination, DNA flow cytometry (FCM), and DNA fragmentation on agarose gel electrophoresis. Cells pretreated for 24 h with Bryo1 and then exposed to VCR showed an increase in apoptosis compared to cells that were exposed to Bryo1 or VCR alone. We also studied the effects of Bryo1, VCR and their combination on cell growth, @entity588 and @entity876 expression, and inhibition of cell proliferation as measured by @entity665 incorporation. Cell analysis showed significant growth inhibition of WSU-DLCL2 cells by the Bryo1/VCR combination as compared to either agent alone. Immunocytochemistry (ICC) revealed that relative @entity588 oncoprotein expression was decreased in cells treated with Bryo1, or VCR separately and was abolished by combining both drugs. When examined by ICC, WSU-DLCL2 cells were initially negative for the @entity876 protein. However, upon treatment with the above agents, the relative expression of @entity876 was moderate on Bryo1-or VCR-treated cells and strong on cells treated with the Bryo1/VCR combination. Cell proliferation as measured by @entity665 incorporation revealed significant inhibition of @entity5 growth by exposure to the agents when compared to the control. In contrast, Bryo1, VCR and their combination did not show any inhibition of normal bone marrow growth. These findings taken together, suggest that the exposure of WSU-DLCL2 cells to Bryo1 prior to treatment with VCR enhances apoptosis, a phenomenon which might be exploited for future therapies.
