DIFFERENTIAL-EFFECTS OF BRYOSTATIN-1 ON HUMAN NON-HODGKINS B-LYMPHOMA CELL-LINES

Bryostatin 1 (Bryo1), a macrocyclic lactone and a protein kinase C activator, is extracted and purified from the marine bryozoan Bugula neritina. In this study we describe its effect on morphology, surface immunophenotype, acid phosphatase (AcP), tartrate-resistant acid phosphatase (TRAP), proliferation and cell cycle of non-Hodgkin's B-lymphoma cell lines representing four differentiation stages. Except for the WSU-BL, a high-grade SCNCL, all other cell lines showed obvious changes in their morphology when treated with 200 nM Bryo1. Phenotypically, a dramatic decrease of CD10 and induction of CD11c and BL7 on some cell lines consistent with further B-cell differentiation was seen. The lines in control cultures showed variable expression of AcP and TRAP. Following treatment with Bryo1, there was a general increase in AcP expression except in WSU-BL line. WSU-FSCCL and WSU-DLCL were TRAP-negative but became TRAP-positive when treated with Bryo1. Cell growth and cycle analysis during treatment of different cell lines revealed evidence of strong, moderate, or no growth inhibition by Bryo1 compared with control cultures. Our results indicate that Bryo1 shows differentiation effects on low-grade FSCCL, intermediate-grade FLCL and high-grade DLCL, and stimulatory or no effect on high-grade SCNCL. Since Bryo1 does not have tumor-promoting activity, it has a potential therapeutic role as a B-cell differentiating agent.