Abstract
Human liposarcoma is the most common soft tissue sarcoma. There is no effective therapy so far except for surgery. In this study, we report for the first time that curcumin induces endoplasmic reticulum (ER) stress in human liposarcoma cells via interacting with sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 2 (SERCA2). Curcumin dose-dependently inhibited the cell survival of human liposarcoma cell line SW872 cells, but did not affect that of human normal adipose-derived cells. Curcumin-mediated ER stress via inhibiting the activity of SERCA2 caused increasing expressions of CHOP and its transcription target death receptor 5 (TRAIL-R2), leading to a caspase-3 and caspase-8 cascade-dependent apoptosis in SW872 cells in vitro and in vivo. Moreover, 70% of human liposarcoma tissues showed an elevated SERCA2 expression compared with normal adipose tissues. Curcumin dose-dependently inhibited the activity of SERCA2, and the interaction of molecular docking and colocalization in ER of curcumin with SERCA2 were further observed. These findings suggest that curcumin may serve as a potent agent for curing human liposarcoma via targeting SERCA2.
Highlights
Liposarcoma is the most common soft tissue sarcoma and accounts for at least 20% of all sarcomas in adults [1]
To find an effective drug therapy for liposarcoma, we report for the first time that curcumin induced endoplasmic reticulum (ER) stress in human liposarcoma cell line SW872 cells via inhibiting the activity of sarcoplasmic/endoplasmic reticulum Ca2þATPase2 (SERCA2), which resulted in CHOPmediated apoptosis
The results revealed that doxorubicin, cisplatin, and sunitinib showed a dose-dependent inhibition of both liposarcoma cells and adipose-derived cells whereas sorafenib and nutlin-3 did not show any inhibition of both cells at the concentrations used
Summary
Liposarcoma is the most common soft tissue sarcoma and accounts for at least 20% of all sarcomas in adults [1]. Surgery serves as the main effective therapy for localized liposarcoma so far and there are few effective treatment options [3]. Patients with liposarcoma often suffer from a high risk of relapse locally in cases of incomplete resection. The local relapse of liposarcoma may usually accompany dedifferentiation and metastasis. The newly developed molecular-targeted agents have been hardly applied for the treatment of liposarcoma in the present time. A basic research of the targeted drug sorafenib found that liposarcoma cell lines were completely resistant to sorafenib treatment [5]
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