Flammulina velutipes polysaccharides (FVP) have been proven to induce apoptosis in HepG2 cells. It is well known that endoplasmic reticulum stress (ERS) is involved in apoptosis. However, ERS mediates FVP-induced apoptosis in HepG2 cells remains unclear. In our study, the results indicated that FVP caused ERS in HepG2 cells. They showed that FVP were water-soluble polysaccharides with the weight average molecular weight of 1972 kDa, which were mainly composed of mannose, gluconic acid, glucose, galactose, xylose and fructose in a molar ratio of 6.6 : 1.3 : 79.9 : 7.4 : 3.4 : 1.5. After FVP treatment, the expression levels of genes and proteins related to ERS were upregulated. The inhibition of ERS by 4-phenylbutyric acid (4-PBA) pretreatment could significantly reduce the role of FVP in inducing apoptosis. We further found the results of immunofluorescence and flow cytometry showing that Ca2+ in the ERS leaked out, and the intracellular Ca2+ concentration increased after FVP treatment. The pretreatment with the phospholipase C (PLC) inhibitor U73122 proved that FVP caused excessive intracellular Ca2+ concentration by activating the phospholipase C-inositol-1,4,5-triphosphate (PLC-IP3) pathway, resulting in ERS, and ultimately leading to apoptosis. In summary, our results indicated that FVP induced ERS-mediated apoptosis by activating PLC-IP3 pathway in HepG2 cells. PRACTICAL APPLICATION: This work may suggest that FVP could be used as an adjuvant therapy to anticancer drugs, providing new application prospects and possibilities.
Keywords: Flammulina velutipes polysaccharides; HepG2 cells; apoptosis; endoplasmic reticulum stress.
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