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

Abstract

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. TGFβ signaling and overexpression of Slug are regarded as the critical events in lung tumor malignancy. Functional studies revealed that SGA inhibited the TGFβ/FAK/AKT axis by inducing lipid-raft-mediated lysosome-dependent TGFβ receptor degradation, resulting in suppressing cancer cell viability and migration. Moreover, SGA elimination of TGFβ-mediated intracellular signaling promoted Slug degradation in H1975 cells. Mechanistically, we demonstrated that proteasome-dependent Slug degradation was controlled by TGFβ-mediated downstream signaling pathways; however, inhibitors of AKT and GSK3 abolished Slug degradation. Our findings suggested that SGA targets of the TGFβ/AKT/GSK3β 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.

Keywords: Antrodia cinnamomea; GSK3β and Slug; Sulfated glucan; TGFβ receptor.