Gossypol On Experimental Studies Of The Role Of Multiple Myeloma,

Background and objective:Multiple myeloma is a clonal plasma cell malignancy disease. The pathogenisis is not clearly clarified yet. Although new therapeutic modalities were developed in recent years, the overall survival has not been improved. Bcl-2 is always overexpressed in most myeloma. It is now recognized that overexpression of Bcl-2/Bcl-xL in cancer cells plays an important role in the development of tumor and chemoresistance. Thus targeting Bcl-2/Bcl-xL is a promising therapeutic strategy for the treatment of cancer. Gossypol is a naturally occurring polyphenolic compound extracted from cotton plants. From 1960s, gossypol had been shown to possess antineoplastic activity against a variety of malignangt celltypes. It could inhibit tumor cell proliferation, induce tumor cell apoptosis, and enhance the sentivity of cancer cell to chemotherapy. Gossypol is also demonstrated well-tolerated and achieving a little effects in some clinical trials, but the mechanisims are not well understood. Recent researches reveal that gossypol is a nonpeptidic small-molecule inhibitor of Bcl-2/Bcl-xL. It can bind to BH3 (Bcl-2 homology domain 3) binding site in Bcl-2/Bcl-xL, and then block the heterodimerization of Bcl-2/Bcl-xL with proapoptotic members in the Bcl-2 protein family such as Bad, Bak, Bid and Bas. It has not been reported about the effect of gossypol in multiple myeloma. In this study, we investigated the antitumor activity of gossypol in vitro and in a Balb/c mouse xenograft model bearing the Wusl cell line. We will also compare the effect of gossypol acetate and apogossypol, and dicuss the possible molecular mechanism.Methods:lTrypan blue staining was used to study the antiproliferatioin of gossypol on multiple myeloma.2 In this study, the apoptosis was determined by Wright-Giemsa staining,...