Naringenin Induces HepG2 Cell Apoptosis via ROS-Mediated JAK-2/STAT-3 Signaling Pathways

Area of Science:

• Hepatocellular carcinoma research
• Cancer biology
• Natural product pharmacology

Background:

• Hepatocellular carcinoma (HCC) is a prevalent cancer with limited treatment options.
• Naringenin, a citrus flavonoid, shows potential anticancer effects, but its mechanisms in HCC are unclear.
• Understanding naringenin's impact on oxidative stress and apoptosis in HCC cells is crucial.

Purpose of the Study:

• To investigate the cytotoxic and anticancer mechanisms of naringenin in HepG2 hepatocarcinoma cells.
• To elucidate the role of oxidative stress in naringenin-induced cell death.
• To explore the effects of naringenin on apoptosis-related signaling pathways.

Main Methods:

• HepG2 cells were treated with naringenin.
• Apoptosis was assessed using flow cytometry (sub-G1 population, phosphatidylserine exposure, mitochondrial potential), DNA fragmentation assays, and caspase activation (caspase-3, caspase-9).
• Intracellular reactive oxygen species (ROS) levels and JAK-2/STAT-3 signaling pathway activity were analyzed.

Main Results:

• Naringenin induced significant apoptosis in HepG2 cells, evidenced by increased sub-G1 population, phosphatidylserine externalization, mitochondrial dysfunction, and DNA fragmentation.
• Naringenin treatment led to the activation of caspase-3 and caspase-9.
• Naringenin enhanced cytotoxicity by increasing intracellular ROS and inhibiting the JAK-2/STAT-3 signaling pathway, further promoting apoptosis.

Conclusions:

• Naringenin effectively induces apoptosis in hepatocarcinoma cells through multiple mechanisms, including oxidative stress induction and JAK-2/STAT-3 pathway inhibition.
• Naringenin demonstrates significant cytotoxic effects on HepG2 cells.
• Naringenin holds promise as a potential therapeutic agent for liver cancer treatment.