Evaluation of the Effect of Perfluorohexane Sulfonate on the Proliferation of Human Liver Cells

Kyeong Hwa Sim, Hyeon Seo Oh, Chuhee Lee, Heesoo Eun () and Youn Ju Lee ()
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Kyeong Hwa Sim: Department of Pharmacology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea
Hyeon Seo Oh: Department of Neurology, Daegu Catholic University Medical Center, Daegu 42472, Republic of Korea
Chuhee Lee: Department of Biochemistry & Molecular Biology, School of Medicine, Yeungnam University, Daegu 42415, Republic of Korea
Heesoo Eun: Research Center for Advanced Analysis, National Agriculture and Food Research Organization (NARO), Tsukuba 305-8604, Japan
Youn Ju Lee: Department of Pharmacology, School of Medicine, Daegu Catholic University, Daegu 42472, Republic of Korea

IJERPH, 2023, vol. 20, issue 19, 1-8

Abstract: Perfluorohexane sulfonate (PFHxS) is a widely detected replacement for legacy long-chain perfluoroalkyl substances (PFAS) in the environment and human blood samples. Its potential toxicity led to its recent classification as a globally regulated persistent organic pollutant. Although animal studies have shown a positive association between PFHxS levels and hepatic steatosis and hepatocellular hypertrophy, the link with liver toxicity, including end-stage liver cancer, remains inconclusive. In this study, we examined the effects of PFHxS on the proliferation of Hep3B (human hepatocellular carcinoma) and SK-Hep1 (human liver sinusoidal endothelial cells). Cells were exposed to different PFHxS concentrations for 24–48 h to assess viability and 12–14 days to measure colony formation. The viability of both cell lines increased at PFHxS concentrations <200 μM, decreased at >400 μM, and was highest at 50 μM. Colony formation increased at <300 μM and decreased at 500 μM PFHxS. Consistent with the effect on cell proliferation, PFHxS increased the expression of proliferating cell nuclear antigen (PCNA) and cell-cycle molecules (CDK2, CDK4, cyclin E, and cyclin D1). In summary, PFHxS exhibited a biphasic effect on liver cell proliferation, promoting survival and proliferation at lower concentrations and being cytotoxic at higher concentrations. This suggests that PFHxS, especially at lower concentrations, might be associated with HCC development and progression.

Keywords: perfluorohexane sulfonate; human hepatocellular carcinoma; liver cancer; colony formation; cell-cycle progression (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
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