Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Nov;72(11):848-852.
doi: 10.1038/s41429-019-0216-6. Epub 2019 Aug 2.

Pro-caspase-3 Protects Cells From Polymyxin B-induced Cytotoxicity by Preventing ROS Accumulation

Affiliations

Pro-caspase-3 Protects Cells From Polymyxin B-induced Cytotoxicity by Preventing ROS Accumulation

Takumi Yokosawa et al. J Antibiot (Tokyo). .

Abstract

Polymyxin B (PMB), a last-line antibiotic used against antibiotic-resistant superbugs, causes undesirable cytotoxic side effects. However, its mechanisms remain unknown. In this study, we unexpectedly found that caspase-3, a main executor of apoptosis, plays a protective role in PMB-induced cytotoxicity. Caspase-3 knockout (KO) cells exhibited higher susceptibility to PMB-induced cytotoxicity compared with wild-type (WT) cells, accompanied by increased levels of reactive oxygen species (ROS). Interestingly, co-treatment with the antioxidant N-acetylcysteine (NAC) rescued cell viability to a similar extent as WT cells. Furthermore, PMB failed to facilitate the processing of inactive caspase-3 (pro-caspase-3) into active forms, suggesting that pro-caspase-3 nonenzymatically suppresses PMB-driven ROS accumulation and its cytotoxicity. Thus, our findings that demonstrate the potential ability of PMB to stimulate ROS generation, but which is normally masked by pro-caspase-3-dependent mechanisms, may provide novel insights into the mechanisms of PMB-induced side effects.

Similar articles

See all similar articles

Publication types

Feedback