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Yarrowia lipolytica L-asparaginase inhibits the growth and migration of lung (A549) and breast (MCF7) cancer cells.
- Source :
-
International journal of biological macromolecules [Int J Biol Macromol] 2021 Feb 15; Vol. 170, pp. 406-414. Date of Electronic Publication: 2020 Dec 30. - Publication Year :
- 2021
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Abstract
- L-asparaginase is an enzyme capable of hydrolyzing the asparagine to aspartic acid and ammonia. L-asparaginase is widely used in the treatment of acute lymphoblastic leukemia (ALL) and other cancers. Here, for the first time, the effects of a novel yeast L-asparaginase from Yarrowia lipolytica were studied on human lung (A549) and breast cancer (MCF7) cell lines as the solid cancer cell lines in terms of cell growth and metastasis inhibition. Functional analysis showed the L-asparagine deprivation mediated anti-proliferation effects by apoptosis induction and changes in the expression of target genes involved in apoptosis and migration pathways. The qRT-PCR analysis showed the higher expression levels of pro-apoptosis genes, including Bax, P53, caspase 3, caspase 8, and down-regulation of Bcl-2 anti-apoptotic gene in treated cells. On the other hand, there was no increase in ROS production in the treated cells. However, L-asparaginase treatment was able to significantly induce autophagy activation in A549 cells. Besides, wound healing assay showed that L-asparaginase could considerably inhibit the migration of A549 and MCF7 cells. Taken together, our results suggested that Yarrowia lipolytica L-asparaginase might be considered for enzyme therapy against breast and lung cancers.<br />Competing Interests: Declaration of competing interest The authors declare no conflict of interest.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- A549 Cells
Apoptosis drug effects
Asparaginase chemistry
Autophagy drug effects
Breast metabolism
Breast Neoplasms drug therapy
Cell Line, Tumor
Cell Movement drug effects
Cell Proliferation drug effects
Gene Expression Regulation, Neoplastic drug effects
Humans
Lung metabolism
Lung Neoplasms drug therapy
MCF-7 Cells
Reactive Oxygen Species
Yarrowia chemistry
Asparaginase pharmacology
Yarrowia enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 170
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 33358949
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2020.12.141