期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 146, 期 -, 页码 193-201出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2019.12.156
关键词
Yarrowia lipolytica; Asparaginase; Anticancer; Acute lymphocytic leukemia; Human Burkitt's lymphoma
资金
- National Institute for Medical Research Development (NIMAD) of Iran [979121]
- Immunology Research Center, Tabriz University of Medical Sciences
- University of Maragheh
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. (C) 2019 Elsevier B.V. All rights reserved.
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