Lentinus edodes-derived β-glucan inhibits human cervical cancer progression through a potential target of DMBT1 on HeLa cell

ABSTRACT Based on the reported strong anti-cervical cancer activity of Lentinus edodes-derived β-glucan (LNT), this study further explored the potential target of LNT in HeLa cancer cells. Our findings demonstrate that LNT could specifically bind to the deleted in malignant brain tumor 1 (DMBT1), a potential target on HeLa cytomembrane. The primary driving force for this binding were mainly hydrogen bonding, hydrophobic interactions, and van der Waals forces. LNT significantly up-regulated the expression of DMBT1 in HeLa cells and reduced HeLa cell viability in a concentration-dependent manner, suggesting that LNT might target DMBT1 to inhibit cancer cell growth. Furthermore, the potential mechanism by which LNT targeted DMBT1 to inhibit HeLa cell viability was investigated using a DMBT1-knockdown HeLa cell model. The results show that LNT-induced proliferation inhibition and apoptosis were significantly lower in DMBT1-knockdown HeLa cells than in non-knockdown HeLa cells, indicating that DMBT1 played a key tumor suppressor role in HeLa cells. Meanwhile, after DMBT1 knockdown, LNT-induced inhibition of PI3K/Akt pathway activation was attenuated in vitro and in vivo, suggesting that LNT induced inhibition of PI3K/Akt pathway activation and HeLa cell viability were closely associated with DMBT1. Therefore, this study proposed a novel strategy for treating cervical cancer by enhancing DMBT1 expression via LNT.