Polyphyllin VII induces apoptosis in HepG2 cells through ROS-mediated mitochondrial dysfunction and MAPK pathways

Area of Science:

• Pharmacology
• Molecular Biology
• Oncology

Background:

• Paris polyphylla is a traditional oriental medicine with known anticancer properties.
• Polyphyllin VII (PP7), a saponin from P. polyphylla, exhibits potent anticancer activity.
• The precise molecular mechanisms of PP7's anticancer effects remain largely unelucidated.

Purpose of the Study:

• To investigate the anticancer effects of Polyphyllin VII (PP7) on human liver cancer cells.
• To elucidate the molecular mechanisms underlying PP7-induced apoptosis in hepatocellular carcinoma cells.

Main Methods:

• Cell viability assessed using MTT assay.
• Apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential evaluated via confocal microscopy.
• Western blotting used to analyze apoptotic protein expression.

Main Results:

• PP7 significantly inhibited HepG2 cell growth and induced apoptosis and necrosis.
• PP7 modulated the Bax/Bcl-2 ratio, cytochrome c release, and caspase activation, indicating apoptosis induction via intrinsic and extrinsic pathways.
• PP7 increased intracellular ROS, depolarized mitochondrial membrane potential, and activated MAPK (JNK, ERK, p38) and PTEN/p53 pathways.

Conclusions:

• PP7 induces apoptotic cell death in HepG2 cells through both intrinsic and extrinsic pathways.
• Mitochondrial-mediated ROS generation and activation of MAPK and PTEN/p53 pathways are crucial for PP7's action.
• PP7 demonstrates potential as a therapeutic agent for hepatocellular carcinoma.