Ganoderma lucidum polysaccharides target a Fas/caspase dependent pathway to induce apoptosis in human colon cancer...

Area of Science:

• * Pharmacology
• * Molecular Biology
• * Cancer Research

Background:

• * Ganoderma lucidum polysaccharides (GLP) exhibit anticancer properties.
• * Colon cancer, specifically the HCT-116 cell line, remains a significant health concern.
• * Understanding GLP's mechanism of action is crucial for developing novel cancer therapies.

Purpose of the Study:

• * To investigate the cytotoxic and apoptotic effects of GLP on HCT-116 human colon cancer cells.
• * To elucidate the molecular mechanisms underlying GLP-induced cell death.
• * To explore the role of intracellular calcium and the death receptor pathway in GLP's anticancer activity.

Main Methods:

• * Cell viability assessed using MTT assay.
• * Cell migration evaluated via wound-healing assay.
• * Lactate dehydrogenase (LDH) release and intracellular calcium levels ([Ca(2+)]i) measured using fluorescence assays.
• * Apoptosis observed through scanning and transmission electron microscopy.
• * Caspase-8 activation, and Fas and caspase-3 expression analyzed by Western blotting.

Main Results:

• * GLP treatment significantly reduced HCT-116 cell viability in a dose-dependent manner.
• * GLP inhibited cell migration, altered cell morphology, elevated intracellular calcium, and increased LDH release.
• * GLP induced apoptosis, evidenced by increased caspase-8 activity and up-regulated Fas and caspase-3 expression.
• * These effects were linked to the activation of the death receptor pathway.

Conclusions:

• * GLP demonstrates significant anticancer activity against HCT-116 colon cancer cells.
• * GLP-induced apoptosis is mediated by intracellular calcium release and activation of the death receptor pathway.
• * GLP represents a promising therapeutic agent for colon cancer treatment.