A β‑1,3‑1,6‑glucan from Aureobasidium pullulans enhances apoptotic and autophagic pathways in colorectal cancer cells

Although β‑glucan exhibits various biological activities, the anticancer mechanisms of a low‑molecular‑weight β‑glucan isolated from Aureobasidium pullulans (LMW‑AP‑FBG) in colorectal cancer remain unclear. Therefore, this study investigated the anticancer potential of LMW‑AP‑FBG in human colon cancer cells. Treatment of SW480 cells with LMW‑AP‑FBG resulted in a significant reduction in cell viability in a concentration‑ and time‑dependent manner, with half‑maximal inhibitory concentrations (IC50) of 557.2, 497.4 and 300.6 µg/ml at 24, 48 and 72 h, respectively. Apoptotic cell death was evidenced by increased caspase‑3/7 enzymatic activity and proteolytic cleavage of caspase‑3, ‑7, ‑8, ‑9 and poly (ADP‑ribose) polymerase. Notably, pharmacological inhibition of caspases using the pan‑caspase inhibitor Z‑VAD‑FMK only partially restored cell viability, suggesting the involvement of caspase‑independent cell death mechanisms. Mitochondrial dysfunction was further indicated by dissipation of mitochondrial membrane potential, cytosolic accumulation of cytochrome c, and downregulation of the anti‑apoptotic protein Bcl‑2, collectively supporting activation of the intrinsic apoptotic pathway. In parallel, the expression of autophagy‑related proteins was markedly increased, implying concomitant induction of autophagic processes. Mechanistically, LMW‑AP‑FBG suppressed the PI3K/AKT/mTOR signaling axis, a central regulator of cell survival and autophagy. Collectively, these findings demonstrate that LMW‑AP‑FBG exerts anticancer effects in SW480 colon cancer cells through coordinated activation of apoptotic and autophagy‑associated pathways, highlighting its potential as a bioactive anticancer agent and warranting further in vivo validation.