title: Targeting sarcoplasmic/endoplasmic reticulum Ca²+-ATPase 2 by curcumin induces ER stress-associated apoptosis for treating human liposarcoma.
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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Lingxian
authors.initials: L
authors.lastname: Wang
authors.forename: Ran
authors.initials: R
authors.lastname: Song
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Gu
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000378:metabolism / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008080:Liposarcoma / Q000188:drug therapy / Q000201:enzymology*; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D013312:Stress, Physiological / Q000187:drug effects*; D051742:Transcription Factor CHOP / Q000235:genetics
chemical_list: C497249:DDIT3 protein, human; D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; D051742:Transcription Factor CHOP; D053148:Caspase 3; D053181:Caspase 8; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D003474:Curcumin