Cancer is one of the most significant health challenges worldwide. Lentinan, a β-glucan from shiitake mushroom, Lentinula edodes, has been demonstrated to have an inhibitory effect on selected cancer cells, but results are inconclusive. The aim of the present study was to investigate the anti-proliferative effect of lentinan on breast adenocarcinoma cells (MCF-7), prostate carcinoma (DU-145), and ovarian carcinoma (SKOV3) using MTS (3-(4,5-dimethylthiazol-2-yl)-5—(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and explore possible mechanisms of action of this compound. In the MCF-7 cells that were used as a positive control, lentinan without phenol red resulted in a significant inhibition of cell viability by 96% while in the presence of phenol red, the weak estrogen effect attributable to phenol red eliminated the significant inhibitory effect of lentinan. Treatment of DU-145 cells with different doses of lentinan resulted in up to a 42% inhibition in cell growth. In SKOV3 cells, lentinan induced a biphasic response where doses of 800 µg/ml or less increased cell viability by 76% – 148%; however, a dose of 1.6 mg/ml inhibited cell proliferation significantly by 87%. When SKOV3 cells were co-treated with lentinan (800 µg/ml or less) and laminarin (a Dectin-1 receptor antagonist), the proliferation-promoting effect of lentinan was dominant over the proliferation-inhibiting effect of laminarin. However, when lentinan was presented at significant higher levels (1600 µg/ml), the inhibitory effect of the two agents became additive in suppressing SKOV3 cell proliferation. Lentinan induced a biphasic response in human ovarian surface epithelial cells (HOSEpC) similar to SKOV3 cells, where the highest dose (1600 µg/ml) resulted in the inhibition of cell growth by 53%. Western blots after treatment of SKOV3 cells with 1600 µg/ml of lentinan demonstrated caspase-3 activation and a decreased anti-apoptotic protein Bcl-2 levels. Our findings reveal that lentinan can be considered as a potential anti-cancer drug for effective treatment of breast and prostate cancer.

Citation Format: Titus Sombuor, Kenneth Shane Broughton, Michael Bergel. Anti-proliferative effects of lentinan, a beta-glucan from shiitake mushroom (lentinula edodes) [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A033.