title: Different anticancer effects of Saxifragifolin A on estrogen receptor-positive and estrogen receptor-negative breast cancer cells.
abstract: BACKGROUND
  Breast cancer is the leading cause of cancer-related death among women worldwide. For treating breast cancer, numerous natural products have been considered as chemotherapeutic drugs.
  
  
  OBJECTIVE
  The present study aims to investigate the apoptotic effect of Saxifragifolin A (Saxi A) isolated from Androsace umbellata in two different human breast cancer cells which are ER-positive MCF-7 cells and ER-negative MDA-MB-231 cells, and examine the molecular basis for its anticancer actions.
  
  
  METHODS
  The inhibitory effects of Saxi A on cell survival were examined in MCF-7 cells and MDA-MB-231 cells in vitro.
  
  
  METHODS
  MTT assays, Annexin V/PI staining analysis, ROS production assay, Hoechst33342 staining and Western blot analysis were performed.
  
  
  RESULTS
  Our results showed that MDA-MB-231 cells were more sensitive to Saxi A-induced apoptosis than MCF-7 cells. Saxi A induced apoptosis in MDA-MB-231 cells through ROS-mediated and caspase-dependent pathways, whereas treatment with Saxi A induced apoptosis in MCF-7 cells in a caspase-independent manner. In spite of Saxi A-induced activation of MAPKs in both breast cancer cell lines, only p38 MAPK and JNK mediated Saxi A-induced apoptosis. In addition, cell survival of shERα-transfected MCF-7 cells was decreased, while MDA-MB-231 cells that overexpress ERα remained viable.
  
  
  CONCLUSIONS
  Saxi A inhibits cell survival in MCF-7 cells and MDA-MB-231 cells through different regulatory pathway, and ERα status appears to be important for regulating Saxi A-induced apoptosis in breast cancer cells. Thus, Saxi A may have a potential therapeutic use for treating breast cancer.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do, 440-746, Republic of Korea.
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do, 440-746, Republic of Korea.
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do, 440-746, Republic of Korea.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Kwak
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do, 440-746, Republic of Korea.. Electronic address: snpyo@skku.edu.
authors.forename: Suhkneung
authors.initials: S
authors.lastname: Pyo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D017382:Reactive Oxygen Species; D012503:Saponins; C000601974:saxifragifolin A; D020169:Caspases
keywords: ER α; MAPK; MCF-7 cell; MDA-MB-231 cell; ROS; Saxifragifolin A