thapsigargin and Adrenocortical-Carcinoma

Thapsigargin (TG) is a natural product that exists in most parts of the plant. In this study, two human ACC cell lines including SW-13 and NCI-H295R were employed to explore the potential role of TG in ACC. A mouse xenograft model of SW-13 cells was established to verify the role of TG in vivo. The cell viability was tested using Cell Counting Kit-8 and Transwell assays. Flow cytometry and Hoechst 33,258 staining were employed to analyze cell apoptosis. RT-qPCR and Western blot (WB) were performed to explore the underlying mechanism of TG-induced apoptosis in ACC cells.. The results indicated that TG dose-dependently inhibited proliferation, migration and invasion in human ACC cells. TG significantly increased the mitochondrial rate of apoptosis and ER stress activity in ACC cells and suppressed ACC xenograft growth in vivo. In addition, the expression of Jun N-terminal kinase (JNK) signaling-related genes and proteins was upregulated by the treatment with TG.. Our findings suggest that TG inhibits the viability of ACC cells by inducing apoptosis through the activation of JNK signaling. Thus, TG is expected to be a potential candidate for the treatment of ACC.

Topics: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Biological Products; Cell Proliferation; Cell Survival; Drug Screening Assays, Antitumor; Endoplasmic Reticulum Stress; Humans; In Vitro Techniques; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms, Experimental; Thapsia; Thapsigargin; Tumor Cells, Cultured