| Gossypol is a naturally occurring polyphenolic compound extracted from the cotton plant of Malvaceae family. It was originally demonstrated as a male antifertility agent and applied in clinic many years ago. In the 1960's, gossypol was identified anticancer efficacy, but the mechanism of which was not known. In the last few years, gossypol has been approved to have antiproliferative and apoptosis-inducing effects on some kinds of cancer cells in vitro. Very recently, it was discovered that gossypol is a potent small-molecule inhibitor of Bcl-2 and Bcl-Xl proteins. It can binds to Bcl-2/Bcl-Xl in the BH3 (Bcl-2 homology domain 3) binding site and blocking the heterodimerization of Bcl-2/Bcl-XL with proapoptotic proteins, such as Bax, Bak and Bad. Such a blocking of antiapoptotic-proapoptotic protein heterodimerization in turn may inhibit the antiapoptotic function of Bc1-2/Bc1-Xl and induce apoptosis in cancer cells. Bcl-2/Bcl-Xl is known to be crucial antagonists of apoptosis. They can block apoptosis of many kinds of cancer cells and increase their tolerance to chernotherapeutic agents and glucocorticoid. Overexpression of Bcl-2 has been observed in B-cell lymphoma, B-cell acute lymphoblastic leukemia (B-ALL), B-cell chronic lymphocytic leukemia (B-CLL) and correlates closely with the occurrence, progress, recurrence and multidrug-resistance of these malignancies. The effects of gossypol on ALL and CLL cells have not been investigated before. In this study, we will verify if gossypol acetate has growth inhibitory effect and apoptosis-inducing activities in Raji lymphoblastoid cell line and try to elucidate the possible molecular mechanism. We will also investigate the effect of gossypol acetate in freshly isolated leukemia cells from patients diagnosed as ALL and CLL and monocyte cells (MNCS) from normal bone marrow. In addition, we will explore whether gossypol acetate has synergistic effect with dexamethasone, a commonly... |
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