Study the Mechanisms of Apoptosis of Destruxin B Anti-tumor Effect on Human Acute and Chronic Lymphoma

• Main Authors: Ya-Chi Yu, 游雅琪
• Other Authors: Chien-Ho Chen
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/20445389275615434056

碩士 === 臺北醫學大學 === 醫學技術學系 === 95 === Destruxins are second metabolic products form an entomogenous fungus, Mararhuzuim anisopliae. These substances are toxic to insect and have been used as an insecticide for decades. Over thirty analogues of destruxins have been isolated by different laboratories, the one used in this study is Destruxin B (DB). The previous study in our laboratory revealed that DB has potent anti-tumor activity in mouse L5178Y lymphoma cells in DBA/2 mice both in vitro and in vivo experiments. In this report, the Molt-4 human acute lymphoblastic leukemia cell line and the Toledo human non Hodgkin’s lymphoma cell lines was used as a subject to evaluate its anti-tumor activity and study the mechanism of the effect. The initial experimental results showed that DB possesses a potent growth suppression effect on Molt-4 when the doses of DB higher than 5.05 uM and Toledo obviously had suppression cell growth at 1.26 uM DB. Further Annexin V and JC-1 staining experimental results showed that Destruxin B caused Molt-4, Toledo cell death by mitochondrial membrane potential changed to induce apoptosis. From the Western blot experimental results found that the expression of AIF and Bax was increased and that decreased in Bid and Bcl-2 expression in Molt-4 and Toledo cells at 48 hours after DB treatment, thus confirming cell death via mitochondrial membrane potential changed to induce apoptosis. We also found the activation of FADD, caspase 8, caspase 3, thus confirming cell death may via death receptor pathway to induce apoptosis also. In conclusion, the mechanisms of cell apoptosis by DB treatment may be due to change mitochondrial membrane potential and the death receptor pathway.