| Summary: | 碩士 === 亞洲大學 === 生物科技學系碩士班 === 101 === ABSTRACT
Bcr-Abl fusion protein activates tyrosine kinase, resulting in the proliferation of leukemia cells, especially chronic myeloid leukemia (CML) cells. Imatinib mesylate, a selective inhibitor of the Abl tyrosine kinase, is effective as a single-agent therapy for CML. However, resistance has been reported, particularly in patients with advanced-stage disease. Mutations within the Abl kinase domain are a major cause of resistance, demonstrating that Bcr-Abl remains a critical drug target. Recently, Gallic acid (3, 4, 5-trihydroxybenzoic acid, GA), has been shown to potently inhibit Bcr-Abl and induce apoptosis in Bcr-Abl-expressing leukemic cells. In this study, we indicate that GA reduced the viability of CML cell line (T315I cells) in dose dependent manner and changed the morphology of cells. GA also effect on the cell cycle, leading to G0/G1 phase arrest at low doses and G2/M phase arrest at higher doses. We investigated the apoptotic activity induced by GA on T315I cells and the underlying mechanisms including DNA fragmentation and apoptotic bodies. The gene expression results show that GA down-regulates Bcr-Abl gene and cyclin D2 gene, and up-regulates p27 gene in mRNA level. Our findings suggest that GA may offer a potential treatment option for CML independent of IM resistance.
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