Recombinant Bacillus caldovelox Arginase Mutant (BCA-M) Induces Apoptosis, Autophagy, Cell Cycle Arrest and Growth Inhibition in Human Cervical Cancer Cells.
Sai-Fung ChungChi-Fai KimHo-Yin ChowHiu-Chi ChongSuet-Ying TamYun-Chung LeungWai-Hung LoPublished in: International journal of molecular sciences (2020)
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.
Keyphrases
- cell cycle arrest
- endothelial cells
- cell death
- clinical trial
- induced pluripotent stem cells
- endoplasmic reticulum stress
- oxidative stress
- pluripotent stem cells
- phase iii
- stem cells
- nitric oxide
- signaling pathway
- open label
- gene expression
- emergency department
- randomized controlled trial
- cell proliferation
- young adults
- recombinant human
- drug induced
- phase ii
- adverse drug
- transcription factor
- amino acid
- case control