Dodecanoic acid induces oxidative stress-mediated death in liver cancer cells through the mitochondrial pathway

Xiaoguang Chen; Qiongxia Lv; Haonan Li; Zhe Wang

doi:10.14393/BJ-v40n0a2024-71135

Authors

Xiaoguang Chen Henan University of Science and Technology https://orcid.org/0000-0002-3928-4333
Qiongxia Lv Henan University of Science and Technology
Haonan Li Henan University of Science and Technology
Zhe Wang Henan University of Science and Technology

DOI:

https://doi.org/10.14393/BJ-v40n0a2024-71135

Keywords:

Cell apoptosis, Dodecanoic acid, Liver tumor, Medium chain fatty acid, Oxidative stress.

Abstract

It has been reported that dodecanoic acid (DDA) exerts anticancer effects on cancers of the reproductive system and digestive system. However, its role in liver cancer and its potential mechanism have rarely been defined. Therefore, in this study, Hepa 1-6 liver cancer cells were incubated with different DDA concentrations (0.1, 0.3, 0.5, 1, 2, 4 mM) for 24, 48 and 72h, and the optimal DDA concentration was determined via a cell viability test. Apoptosis and cell cycle distribution were determined by flow cytometry. SOD activity, mitochondrial membrane potential (MMP), ATP, GSH and ROS levels were measured by commercial assay kits; Bcl-2, Bax and Caspase-3 protein levels were analyzed by western blot. The results showed that 0.5 mM DDA decreased cell viability in a time-dependent manner, so this concentration was used to investigate how DDA leads to Hepa 1-6 cell apoptosis. After treatment with DDA, a significant, time-dependent increase in the cell apoptotic rate was detected despite the accumulation of S-phase cells. The increased ROS levels and decreased GSH levels and SOD activity in DDA-treated cells indicated the occurrence of oxidative stress. Mitochondrial dysfunction was evidenced by a decreased MMP and reduced ATP levels. Cell apoptotic death via the mitochondrial pathway was indicated by a reduced Bcl-2/Bax ratio and increased caspase-3 protein levels. It can be concluded that DDA can effectively trigger liver cancer cell death by inducing oxidative stress and disrupting mitochondrial function. These findings provide new insight into the potential mechanism of action of DDA in liver cancer.

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