Cadmium modulates steatosis, fibrosis, and oncogenic signaling in liver cancer cells by activating notch and AKT/mTOR pathways

• DOI: 10.1002/tox.23731
• Publication Date: 2023-01-05T14:19:19Z
• Authors: Suryakant Niture; Sashi Gadi; Minghui Lin; Qi Qi; Samiksha S. Niture; John T. Moore; Wanda Bodnar; Reshan A. Fernando; Keith E. Levine; Deepak Kumar
• Keywords: Steatosis

Cadmium (Cd) is an environmental pollutant that increases hepatotoxicity and the risk of liver diseases. In current study, we investigated effect a physiologically relevant, low concentration Cd on regulation cancer cell proliferation, steatosis, fibrogenic/oncogenic signaling. Exposure to concentrations increased endogenous reactive oxygen species (ROS) production enhanced proliferation in human bipotent progenitor line HepaRG hepatocellular carcinoma (HCC) lines. Acute exposure Jagged-1 expression activated Notch signaling HCC cells HepG2 SK-Hep1. AKT/mTOR by increasing phosphorylation AKT-S473 mTOR-S-4448 residues. Moreover, also promoted steatosis induced fibrogenic cells. Chronic Cd-activated pro-inflammatory cytokines tumor necrosis factor-alpha (TNFα) its downstream target TNF-α-Induced Protein 8 (TNFAIP8). RNA-Seq data revealed chronic modulated several fatty disease-related genes involved steatosis/fibrosis Collectively, our suggest modulate along with oncogenic activating pathways.