Polysaccharides from sporoderm‑removed spores of Ganoderma lucidum induce apoptosis in human gastric cancer cells via disruption of autophagic flux

Abstract

The sporoderm-broken spores of Ganoderma lucidum (G. lucidum) polysaccharide (BSGLP) have been demonstrated to inhibit carcinogenesis in several types of cancer. However, to the best of our knowledge, the anticancer effects of polysaccharides extracted from the newly developed sporoderm-removed spores of G. lucidum (RSGLP) have not been assessed. The present study first compared the anticancer effects of RSGLP and BSGLP in three gastric cancer cell lines and it was found that RSGLP was more potent than BSGLP in decreasing gastric cancer cell viability. RSGLP significantly induced apoptosis in AGS cells, accompanied by downregulation of Bcl-2 and pro-caspase-3 expression levels, and upregulation of cleaved-PARP. Furthermore, RSGLP increased LC3-II and p62 expression, indicative of induction of autophagy and disruption of autophagic flux in AGS cells. These results were further verified by combined treatment of AGS cells with the late-stage autophagy inhibitor chloroquine, or early-stage autophagy inducer rapamycin. Adenoviral transfection with mRFP-GFP-LC3 further confirmed that autophagic flux was inhibited by RSGLP in AGS cells. Finally, the present study demonstrated that the RSGLP-induced autophagy and disruption of autophagic flux disruption was, at least in part, responsible for RSGLP-induced apoptosis in AGS cells. The results of the present study demonstrated for the first time that RSGLP is more effective than BSGLP in inhibiting gastric cancer cell viability, and RSGLP may serve as a promising autophagy inhibitor in the management of gastric cancer.

Sporoderm-Removed Ganoderma lucidum Spore Powder May Suppress the Proliferation, Migration, and Invasion of Esophageal Squamous Cell Carcinoma Cells Through PI3K/AKT/mTOR and Erk Pathway

“…Emerging evidence suggests that sporoderm-removed Ganoderma lucidum spore powder has great potential in the treatment of human cancers. 8 In this study, we found that sporoderm-removed Ganoderma lucidum spore powder inhibited the proliferation of esophageal squamous cell carcinoma KYSE140 and KYSE510 cells in a dose-dependence and time-dependence.…”

“… 6 , 7 Interestingly, sporoderm-removed Ganoderma lucidum spore powder, which contains much more polysaccharide and triterpenoids than Ganoderma lucidum spore and sporoderm-broken Ganoderma lucidum spores, has demonstrated antitumor activities in both in vivo and vitro studies. 8 , 9 However, the anti-cancer effect and mechanism of sporoderm-removed Ganoderma lucidum spore powder in esophageal squamous cell carcinoma has not been clarified.…”

Research Progress on the Anticancer Activities and Mechanisms of Polysaccharides From Ganoderma

“…GLP was capable of repressing azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis and colorectal carcinogenesis in mice (Guo C. et al, 2021). Mechanistically, GLP reversed gut microbiota dysbiosis caused by AOM/DSS.…”

“…The metabolites of intestinal microbes including SCFAs play a critical role in preserving intestinal homeostasis. The fecal levels of SCFAs including acetate, butyrate and propionate were reduced in AOM/DSS-treated mice, whereas GLP reversed their downregulation (Guo C. et al, 2021). Besides, GLP treatment markedly elevated the expression of G proteincoupled receptor 43 (GPR43) in colonic cells that specifically FIGURE 2 | The roles of Ganoderma polysaccharides in modifying antitumor immunity.…”

“…Zhong et al Zhong et al (2021 ) compared the anticancer activities of polysaccharides from sporoderm-removed spores (RSGLP) and sporoderm-broken spores of G. lucidum (BSGLP). RSGLP showed stronger inhibitory activity against gastric cancer cell viability than BSGLP.…”