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چکیده
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l-Asparaginase (l-asparagine amidohydrolase; E.C.3.5.1.1) as an anticancer agent is used to treat acute lymphocytic leukemia (ALL), Human Burkitt's lymphoma and non-Hodgkin's lymphoma. The commercial asparaginases are obtained from bacteria Erwinia chrysanthemi and Escherichia coli now which had many side effects. In this study, the effects of a novel l-asparaginase from yeast Yarrowia lipolytica was investigated on human ALL and Burkitt's lymphoma cell lines. The l-asparaginase causes metabolic stress, cytotoxicity, and apoptosis due to the arrest of the G0 cell cycle, the activation of caspase-3 and the modulation of mitochondrial membrane integrity. The RT-PCR analysis showed a significant increase in the pro-apoptosis genes such as Bax, Caspase-3, Caspase-8, Caspase-9 and p53 (P < 0.05) while the anti-apoptotic marker Bcl-2 was significantly decreased (P < 0.05). Furthermore, Y. lipolytica l-asparaginase causes autophagy and increased ROS. The l-asparaginase has cytotoxic and anticancer effects higher than commercial asparaginase. In conclusion, Y. lipolytica l-asparaginase shows interesting anticancer activity and it can be introduced as a new eukaryotic and therapeutic agent and strategy for ALL and Burkitt's lymphoma treatment after the in vivo and clinical experiments.
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