The β-glucan fromLentinus edodessuppresses cell proliferation and promotes apoptosis in estrogen receptor positive breast cancers

Abstract

Breast cancer is now the most common cancer in worldwide women, and novel interventions are needed to overcome the resistance occurring in the estrogen-targeted endocrine therapy. Herein, we demonstrate that the β-glucan from Lentinus edodes (LNT) exhibited a profound inhibition ratio of ∼53% against estrogen receptor positive (ER+) MCF-7 tumor growth in nude mice similar to the positive control of cisplatin. Immunohistochemistry images showed that LNT evidently suppressed cell proliferation and promoted apoptosis in MCF-7 tumor tissues. The Western blotting analysis indicated that LNT up-regulated the tumor suppressor p53, phosphorylated extracellular signal-regulated kinase1/2 (p-ERK1/2), cleaved-Caspase 3 and poly [ADP (ribose)] polymerase 1 (PARP 1) protein levels, and reduced the expression of mouse double minute 2 (MDM2), telomerase reverse transcriptase (TERT), nuclear factor-kappa B (NF-κB) p65, B-cell lymphoma-2 (Bcl-2), estrogen receptor α (ERα), etc. in tumor tissues. Moreover, LNT significantly suppressed phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt) and mammalian target of rapamycin (mTOR) protein levels. It was thus proposed that LNT inhibited MCF-7 tumor growth through suppressing cell proliferation and enhancing apoptosis possibly via multiple pathways such as PI3K/Akt/mTOR, NF-κB-, ERK-, ERα-, caspase- and p53-dependent pathways. Interestingly, the cell viability assay, siRNA transfection, Western blotting and flow cytometric analysis suggested that LNT targeted p53/ERα to only suppress cell proliferation via cell cycle arrest at G2/M phase without apoptosis in vitro. The big difference between in vivo and in vitro data suggested that the immune responses triggered by the polysaccharide should mainly contribute to the apoptotic effect in vivo. Overall, this work provides a novel strategy to treat ER+ breast cancers by using a naturally occurring β-glucan from mushrooms.

The protective effects of total paeony glycoside on ischemia/reperfusion injury in H9C2 cells via inhibition of the PI3K/Akt signaling pathway

“…Previous studies have suggested that the PI3K/Akt signaling pathway is involved in the apoptosis of various tumor cells ( 41 , 42 ). Furthermore, it has been revealed that certain drugs could decrease apoptosis and oxidative stress of cells via regulation of the PI3K/Akt signaling pathway ( 41 , 43 , 44 ).…”

Beta Glucan: Supplement or Drug? From Laboratory to Clinical Trials

“…In fact, numerous animal and human studies have shown remarkable activity against a wide variety of tumors [19,40,41,42,43]. Further, more recent studies have repeatedly shown that glucan has a strong synergy with the antibodies which naturally occur in cancer [19,44,45].…”

Laminarin from Seaweed (Laminaria japonica) Inhibits Hepatocellular Carcinoma Through Upregulating Senescence Marker Protein-30

“…For example, b-glucan from Lentinus edodes inhibits tumor growth in mice by suppressing the proliferation and enhancing the apoptosis of MCF-7 breast cancer cells. 18 (1 / 3)-b-D-glucan from Saccharomyces cerevisiae significantly decreases the volume and weight of S180 tumors in mice. 19 b-glucan from the Maitake mushroom induces the apoptosis of prostate cancer PC-3 cells.…”