2. Academic Validation
  3. Acesulfame potassium upregulates PD-L1 in HCC cells by attenuating autophagic degradation

Acesulfame potassium upregulates PD-L1 in HCC cells by attenuating autophagic degradation

  • Biochem Biophys Res Commun. 2024 Jun 4:711:149921. doi: 10.1016/j.bbrc.2024.149921.
Dong-Ho Kim 1,  Eun-Jun Kwon 1,  Keun-Gyu Park 2,  Jonghwa Jin 3,  Jun-Kyu Byun 4
Affiliations

Affiliations

  • 1 Department of Biomedical Science, Kyungpook National University, Daegu, 41566, South Korea.
  • 2 Department of Biomedical Science, Kyungpook National University, Daegu, 41566, South Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, South Korea; Research Institute of Aging and Metabolism, Kyungpook National University, Daegu, 41566, South Korea.
  • 3 Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, South Korea. Electronic address: becauseofu77@gmail.com.
  • 4 BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu, 41566, South Korea. Electronic address: jkbyun@knu.ac.kr.
PMID: 38603831 DOI: 10.1016/j.bbrc.2024.149921
Abstract

Artificial Sweeteners, which contain no or few calories, have been widely used in various foods and beverages, and are regarded as safe alternatives to sugar by the Food and Drug Administration. While several studies suggest that artificial Sweeteners are not related to Cancer development, some research has reported their potential association with the risk of cancers, including hepatocellular carcinoma (HCC). Here, we investigated whether acesulfame potassium (Ace K), a commonly used artificial sweetener, induces immune evasion of HCC cells by upregulating programmed death ligand-1 (PD-L1). Ace K elevated the protein levels of PD-L1 in HCC cells without increasing its mRNA levels. The upregulation of PD-L1 protein levels in HCC cells by Ace K was induced by attenuated autophagic degradation of PD-L1, which was mediated by the Ace K-stimulated ERK1/2-mTORC1 signaling pathway. Ace K-induced upregulation of PD-L1 attenuated T cell-mediated death of HCC cells, thereby promoting immune evasion of HCC cells. In summary, the present study suggests that Ace K promotes HCC progression by upregulating the PD-L1 protein level.

Keywords

Acesulfame potassium; Artificial sweetener; Autophagy; Hepatocellular carcinoma; Immune evasion; PD-L1.

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