Differential Mechanism of ATP Production Occurs in Response to Succinylacetone in Colon Cancer Cells

Molecules

HeeMin Yoo¹  PhilJun Lee²  HongPyo Kim²  SeungJe Woo²  Namki Cho³ 

[1] Center for Bioanalysis, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Korea;College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 443-749, Korea;College of Pharmacy, Chonnam National University, Gwangju 61186, Korea;

关键词: succinylacetone;    colon cancer cell lines;    apoptosis;    atp;    oxidative phosphorylation;    pyruvate dehydrogenase;   

DOI  :  10.3390/molecules24193575

来源: DOAJ

【 摘 要 】

Our aim was to verify the potential ability of succinylacetone (SA) to inhibit mitochondrial function, thereby suppressing cancer cell proliferation. SA treatment caused apoptosis in HCT116 and HT29 cells, but not in SW480 cells, with mitochondria playing a key role. We checked for dysfunctional mitochondria after SA treatment. Mitochondria of HT29 cells were swollen, indicating damage, whereas in HCT116 cells, several mitochondria had a diminished size. Damaged mitochondria decreased ATP production and induced reactive oxygen species (ROS) in the cells. To understand SA-induced reduction in ATP production, we investigated the electron transfer chains (ETC) and pyruvate dehydrogenase kinase (PDK) activity, which prevents the transfer of acetyl-CoA to the TCA (tricarboxylic acid) cycle by inhibiting PDH (pyruvate dehydrogenase) activity. In each cell line, the inhibitory mechanism of ATP by SA was different. The activity of complex III consisting of the mitochondrial ETCs in HT29 cells was decreased. In contrast, PDH activity in HCT116 cells was reduced. Nicotinamide nucleotide transhydrogenase (NNT)-removing reactive oxygen species (ROS) was upregulated in HT29 cells, but not in HCT116 cells, indicating that in HT29 cells, a defense mechanism was activated against ROS. Collectively, our study showed a differential mechanism occurs in response to SA in colon cancer cells.

【 授权许可】

Unknown