Epibrassinolide activates AKT to trigger autophagy with polyamine metabolism in SW480 and DLD-1 colon cancer cell lines

Abstract

Epibrassinolide (EBR), a plant-derived polyhydroxylated derivative of 5α-cholestane, structurally shows similarities toanimal steroid hormones. According to the present study, EBR treatment triggered a significant stress response via activating ER stress,autophagy, and apoptosis in cancer cells. EBR could also increase Akt phosphorylation in vitro. While the activation of Akt resulted incellular metabolic activation in normal cells to proceed with cell survival, a rapid stress response was induced in cancer cells to reducesurvival. Therefore, Akt as a mediator of cellular survival and death decision pathways is a crucial target in cancer cells. In this study,we determined that EBR induces stress responses through activating Akt, which reduced the mTOR complex I (mTORC1) activation inSW480 and DLD-1 colon cancer cells. As a consequence, EBR triggered macroautophagy and led to lipidation of LC3 most efficientlyin SW480 cells. The cotreatment of spermidine (Spd) with EBR increased lipidation of LC3 synergistically in both cell lines. We alsofound that EBR promoted polyamine catabolism in SW480 cells. The retention of polyamine biosynthesis was remarkable followingEBR treatment. We suggested that EBR-mediated Akt activation might determine the downstream cellular stress responses to induceautophagy related to polyamines.