A sulfated glucan from Antrodia cinnamomea reduces Slug expression through regulation of TGFβ/AKT/GSK3β axis in lung cancer

SGA is a sulfated glucan from Antrodia cinnamomea. In this study, we showed that SGA suppressed tumor growth in vitro and in vivo. SGA also potentiated cisplatin-induced cytotoxicity in lung cancer cells. TGF beta signaling and overexpression of Slug are regarded as the critical events in lung tumor malignancy. Functional studies revealed that SGA inhibited the TGF beta/FAK/AKT axis by inducing lipid-raft-mediated lysosome-dependent TGF beta receptor degradation, resulting in suppressing cancer cell viability and migration. Moreover, SGA elimination of TGF beta-mediated intracellular signaling promoted Slug degradation in H1975 cells. Mechanistically, we demonstrated that proteasome-dependent Slug degradation was controlled by TGF beta-mediated downstream signaling pathways; however, inhibitors of AKT and GSK3 abolished Slug degradation. Our findings suggested that SGA targets of the TGF beta/AKT/GSK3 beta axis played a key role in enhancing Slug degradation and suppressing lung cancer cells. In addition, SGA may be a potential therapeutic supplement for lung cancer.