The Role of Porphyromonas gingivalis in Proliferation, Lipid Accumulation, and Invasion in HepG2 Cells and the Effects of Carnosic Acid

Aim: Porphyromonas gingivalis (Pg), a periodontal pathogen, has been linked to systemic diseases, including cancer. This study investigates the oncogenic effects of Pg and its endotoxin, lipopolysaccharide (LPS), on liver cancer cells and evaluates the potential anti-cancer effects of carnosic acid (CA). Methods: Human liver cancer cell lines (HepG2 and HuH7) and pancreatic cancer cells were treated with Pg at different multiplicities of infection (MOI) or Pg-derived LPS. Cell proliferation was assessed using a viability assay. Western blot analysis was performed to examine the expression of key signaling molecules, including Toll-like receptor (TLR)4, phosphorylated ERK, Akt, NF- ΚB, mTOR, and Nrf2. Lipid accumulation was evaluated using Bodipy fluorescent reagent, and migration and invasion assays were conducted to assess cell motility. Results: Pg promoted proliferation in HepG2 and pancreatic cancer cells in an MOI-dependent manner and upregulated TLR4, ERK, Akt, and NF- ΚB. Pg-derived LPS significantly enhanced cell proliferation, but CA did not show a significant inhibitory effect on this proliferation. In HuH7 cells, CA reduced proliferation via Nrf2 activation, whereas in HepG2 cells, CA did not significantly activate Nrf2 or suppress proliferation. However, CA reduced LPS-induced lipid accumulation and migration in HepG2 cells, partly by modulating mTOR, Akt, and TGF- Β signaling. Conclusions: These findings suggest that Pg promotes oncogenic processes, while CA may exert anti-Pg effects partially in a cell type-specific manner.