Abstract
Ganoderma lucidum polysaccharides (GLP) extracted from Ganoderma lucidum have been shown to induce cell death in some kinds of cancer cells. This study investigated the cytotoxic and apoptotic effect of GLP on HCT-116 human colon cancer cells and the molecular mechanisms involved. Cell proliferation, cell migration, lactate dehydrogenase (LDH) levels and intracellular free calcium levels ([Ca(2+)]i) were determined by MTT, wound-healing, LDH release and fluorescence assays, respectively. Cell apoptosis was observed by scanning and transmission electron microscopy. For the mechanism studies, caspase-8 activation, and Fas and caspase-3 expression were evaluated. Treatment of HCT-116 cells with various concentrations of GLP (0.625-5 mg/mL) resulted in a significant decrease in cell viability (P< 0.01). This study showed that the antitumor activity of GLP was related to cell migration inhibition, cell morphology changes, intracellular Ca(2+) elevation and LDH release. Also, increase in the levels of caspase-8 activity was involved in GLP-induced apoptosis. Western blotting indicated that Fas and caspase-3 protein expression was up-regulated after exposure to GLP. This investigation demonstrated for the first time that GLP shows prominent anticancer activities against the HCT-116 human colon cancer cell line through triggering intracellular calcium release and the death receptor pathway.
Highlights
Colon cancer, which caused by cellular pathology in the appendix, colon, or in the rectum, is the third most common cancer in the world
This study showed that the antitumor activity of Ganoderma lucidum polysaccharides (GLP) was related to cell migration inhibition, cell morphology changes, intracellular Ca2+ elevation and lactate dehydrogenase (LDH) release
Western blotting indicated that Fas and caspase-3 protein expression was up-regulated after exposure to GLP
Summary
Colon cancer, which caused by cellular pathology in the appendix, colon, or in the rectum, is the third most common cancer in the world. Chemotherapy and radiation are typically used before or after surgery in colorectal treatment. The toxicity produced by chemotherapy inflicts on immune system of cancer patients in the course of treatment. Compounds from herbaceous plants are recognized as pharmacological agents to inhibit cancer growth and lessen the side effects of radiation and chemotherapy (Chen et al, 2009; Chen et al, 2010). GLP, isolated from Ganoderma lucidum, have been used in East Asian countries to remedy conditions like aging, oxidation, radiation and hypertension for thousands of years (Chen et al, 2009; Pillai et al, 2010; Li et al, 2011). Previous studies have showed that GLP can mediate cytotoxicity in number of cancer cell lines including lung cancer, prostate cancer and breast cancer.
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