Non-starch polysaccharides from different developmental stages of Pleurotus tuber-regium inhibited the growth of human acute promyelocytic leukemia HL-60 cells by cell-cycle arrest and/or apoptotic induction

The chemical compositions and in vitro anti-proliferative activities of the water-soluble non-starch polysaccharides (NSPs) extracted from the fruiting body, mycelium and culture medium (coded as HWE, EDP and CEP, respectively) of a novel edible mushroom Pleurotus tuber-regium (PTR) were compared. HWE is likely to be a heteropolysaccharide–protein complex with a high molecular weight of 186 × 104. Glucose-rich EDP had a moderate MW of 50.9 × 104 while mannose-rich CEP had a low MW of 4.4 × 104. Among all PTR NSPs, HWE had the strongest cytotoxicity (approximate IC50: 25 μg/ml) and exerted effective anti-proliferative activity at 200 μg/ml against human acute promyelocytic leukemia cells (HL-60). All PTR NSPs induced apoptosis in HL-60 cells with an increase in the ratio of Bax/Bcl-2. Analysis from flow cytometry and Western blot demonstrated that EDP caused G2/M arrest in HL-60 cells by lowering the Cdk1 expression while HWE caused S arrest in the HL-60 cells by a depletion of Cdk2 and an increase in cyclin E expression.