title: Curcumin induces apoptosis by inhibiting sarco/endoplasmic reticulum Ca2+ ATPase activity in ovarian cancer cells.
abstract: Aberrant increase in the expression levels of sarco/endoplasmic reticulum calcium ATPase (SERCA), which regulates Ca(2+) homeostasis, has been observed in ovarian cancers. In this study, we demonstrated that curcumin increases cytosolic Ca(2+) concentration through inhibition of SERCA activity, causing apoptosis in ovarian cancer cells but not in normal cells, including peripheral blood mononuclear cells (PBMCs) and ovarian surface epithelial cells (OSE). Curcumin induced apoptosis in ovarian cancer cells in a concentration- and time-dependent manner. Cytosolic Ca(2+) flux was evident after the curcumin treatment (15 µM). Treatment with Ca(2+) chelator reduced curcumin-induced apoptosis, confirming the possible involvement of increased cytosolic Ca(2+) concentration in this response. Basal mRNA and protein levels of SERCA2 were significantly higher in ovarian cancer cells than in OSE. SERCA activity was suppressed by curcumin, with no effect on protein expression. Forced expression of the SERCA2b gene in ovarian cancer cells prevented curcumin-induced cytosolic Ca(2+) elevation and subsequent apoptosis, supporting an important role of SERCA in curcumin-induced apoptosis of ovarian cancer cells. Taken together, inhibition of SERCA activity by curcumin disrupts the Ca(2+) homeostasis and thereby promotes apoptosis in ovarian cancer cells.
authors.affiliation: WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Jeong-Ah
authors.initials: JA
authors.lastname: Seo
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea; Nano System Institute, Seoul National University, Gwanak-ro, Gwanak-gu, Seoul 151-744, Republic of Korea.
authors.forename: Boyun
authors.initials: B
authors.lastname: Kim
authors.affiliation: Peggy and Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 1417, Oklahoma City, OK 73012, USA.
authors.forename: Danny N
authors.initials: DN
authors.lastname: Dhanasekaran
authors.affiliation: Departments of Obstetrics & Gynecology and Cellular & Molecular Medicine, Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Ontario K1H 8L6, Canada; Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Tsang
authors.affiliation: WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea; Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea. Electronic address: yssong@snu.ac.kr.
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Song
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D065096:Calcium Chelating Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006706:Homeostasis; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D065096:Calcium Chelating Agents; D004791:Enzyme Inhibitors; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D003474:Curcumin; D002118:Calcium
keywords: Apoptosis; Curcumin; Normal ovarian surface epithelial cell; Ovarian cancer; Sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA)