Altered cellular metabolism of HepG2 cells caused by microcystin-LR.
This study aimed to evaluate the possible effects of microcystin-LR (MC-LR) exposure on the metabolism and drug resistance of human hepatocellular carcinoma (HepG2) cells. For this purpose, we first conducted an experiment to make sure that MC-LR could penetrate the HepG2 cell membrane effectively. The transcriptional levels of phase I (such as CYP2E1, CYP3A4, and CYP26B1) and phase II (such as EPHX1, SULTs, and GSTM) enzymes and export pump genes (such as MRP1 and MDR1) were altered by MC-LR-exposure for 24 h, indicating that MC-LR treatment may destabilize the metabolism of HepG2 cells. Further research showed that the CYP inducers omeprazole, ethanol, and rifampicin inhibited cell viability, in particular, ethanol, a CYP2E1 inducer, induced ROS generation, lipid peroxidation, and apoptosis in HepG2 cells treated with MC-LR. The CYP2E1 inhibitor chlormethiazole inhibited ROS generation, mitochondrial membrane potential loss, caspase-3 activity, and cytotoxicity caused by MC-LR. Meanwhile, the results also showed that co-incubation with the ROS scavenger l-ascorbic acid and MC-LR decreased ROS levels and effectively prevented apoptosis. These findings provide an interesting mechanistic explanation of cellular metabolism associated with MC-LR, i.e., MC-LR-exposure exerted toxicity on HepG2 cells and induced apoptosis of HepG2 cells via promoting CYP2E1 expression and inducing excessive ROS in HepG2 cells.
College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China.
Junguo
J
Ma
College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China.
Yiyi
Y
Feng
College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China.
Siyu
S
Jiang
College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China. Electronic address: lixiaoyu65@263.net.
Xiaoyu
X
Li
D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D015227:Lipid Peroxidation; D008387:Marine Toxins; D053078:Membrane Potential, Mitochondrial; D052998:Microcystins / Q000633:toxicity*; D018675:Toxicity Tests
D008387:Marine Toxins; D052998:Microcystins; D053148:Caspase 3; C057862:cyanoginosin LR; D001205:Ascorbic Acid
Drug resistance gene; HepG2; Metabolism-associated enzyme; Microcystin-LR; OATPs