The Nitric Oxide Prodrug JS-K Induces Ca(2+)-Mediated Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Hepatocellular carcinoma (HCC) is a prevalent and lethal human malignancy.
• JS-K, a novel compound, demonstrates potential in inducing tumor cell apoptosis.

Purpose of the Study:

• To investigate the anti-cancer effects of JS-K on HepG2 cells.
• To elucidate the underlying molecular mechanisms of JS-K-induced apoptosis.

Main Methods:

• HepG2 cells were treated with JS-K at various concentrations and time points.
• Apoptosis, cell proliferation, mitochondrial membrane potential, and intracellular calcium levels were assessed.
• Western blotting was used to analyze protein expression (Bax, Bcl-2, caspase-9, caspase-3).
• The roles of nitric oxide (NO) and calcium were evaluated using scavengers and chelators.

Main Results:

• JS-K inhibited HepG2 cell proliferation and induced apoptosis in a dose- and time-dependent manner.
• JS-K treatment led to increased Bax/Bcl-2 ratio, cytochrome c release, and activation of caspase-9/3.
• JS-K elevated cytosolic Ca(2+) and decreased mitochondrial membrane potential.
• Carboxy-PTIO (NO scavenger) and BAPTA-AM (Ca(2+) chelator) attenuated JS-K-induced apoptosis by modulating these pathways.

Conclusions:

• JS-K induces apoptosis in HepG2 cells via a mitochondrial pathway.
• This process is mediated by increased cytosolic Ca(2+) and subsequent caspase activation.
• NO and intracellular calcium play critical roles in JS-K-induced hepatocellular carcinoma cell death.