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Title: | Recombinant bacillus caldovelox arginase mutant (BCA-M) induces apoptosis, autophagy, cell cycle arrest and growth inhibition in human cervical cancer cells | Authors: | Chung, SF Kim, CF Chow, HY Chong, HC Tam, SY Leung, YC Lo, WH |
Issue Date: | 2020 | Source: | International journal of molecular sciences, 2020, v. 21, no. 20, 7445, p. 1-20 | Abstract: | With our recent success in developing a recombinant human arginase drug against broad-spectrum cancer cell lines, we have explored the potential of a recombinant Bacillus caldovelox arginase mutant (BCA-M) for human cervical cancer treatment. Our studies demonstrated that BCA-M significantly inhibited the growth of human cervical cancer cells in vitro regardless of argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) expression. Drug susceptibilities correlate well with the expressions of major urea cycle genes and completeness of L-arginine regeneration pathways. With the expressions of ASS and ASL genes conferring resistance to L-arginine deiminase (ADI) which is undergoing Phase III clinical trial, BCA-M offers the advantage of a broader spectrum of susceptible cancer cells. Mechanistic studies showed that BCA-M inhibited the growth of human cervical cancer cells by inducing apoptosis and cell cycle arrest at S and/or G2 /M phases. Our results also displayed that autophagy served as a protective mechanism, while the growth inhibitory effects of BCA-M could be enhanced synergistically by its combination to the autophagy inhibitor, chloroquine (CQ), on human cervical cancer cells. | Keywords: | Apoptosis Arginase Autophagy Cell cycle arrest Cervical cancer cell |
Publisher: | Molecular Diversity Preservation International (MDPI) | Journal: | International journal of molecular sciences | ISSN: | 1661-6596 | EISSN: | 1422-0067 | DOI: | 10.3390/ijms21207445 | Rights: | © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). The following publication Chung S-F, Kim C-F, Chow H-Y, Chong H-C, Tam S-Y, Leung Y-C, Lo W-H. Recombinant Bacillus caldovelox Arginase Mutant (BCA-M) Induces Apoptosis, Autophagy, Cell Cycle Arrest and Growth Inhibition in Human Cervical Cancer Cells. International Journal of Molecular Sciences. 2020; 21(20):7445, is available at https://doi.org/10.3390/ijms21207445 |
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