title: Sulforaphene Synergistically Sensitizes Cisplatin via Enhanced Mitochondrial Dysfunction and PI3K/PTEN Modulation in Ovarian Cancer Cells.
abstract: OBJECTIVE
  To explore if a natural isothiocyanate, sulforaphene (SFE), sensitizes ovarian cancer cells to the chemotherapy drug cisplatin (CDDP).
  
  
  METHODS
  We studied reactive oxygen species (ROS), mitochondrial membrane depolarization and cell-cycle distribution in two ovarian cancer cell lines SKOV3 and SNU 8 treated with SFE and cisplatin. We further analyzed the expression of caspases 3, 8, and 9, Phosphoinositide 3-kinase (PI3K) and Phosphatase and tensin homolog (PTEN) by western blotting.
  
  
  RESULTS
  SFE sensitized cells to cisplatin by enhancing ROS and mitochondrial membrane depolarization that released cytochrome c and activated caspase 9 and caspase 3 in the mitochondrial pathway. It also inhibited extrinsic pathway protein caspase 8, growth-related protein PI3K and further activated PTEN in combination with cisplatin.
  
  
  CONCLUSIONS
  SFE synergistically inhibited proliferation and induced apoptosis of SKOV3 and SNU8 cells in combination with cisplatin by activating multiple apoptotic pathways. Therefore, we suggest sulforaphene as a chemo-enhancing adjuvant to improve the efficacy of cisplatin in ovarian cancer treatment.
authors.affiliation: Beckman Laser Institute Korea, Dankook University, Cheonan, Republic of Korea Department of Pre-medical Science, Dankook University, Cheonan, Republic of Korea.
authors.forename: Raktim
authors.initials: R
authors.lastname: Biswas
authors.affiliation: Beckman Laser Institute Korea, Dankook University, Cheonan, Republic of Korea Department of Pre-medical Science, Dankook University, Cheonan, Republic of Korea Biomedical Translational Research Institute, Dankook University, Cheonan, Republic of Korea.
authors.forename: Jin-Chul
authors.initials: JC
authors.lastname: Ahn
authors.affiliation: Department of Obstetrics and Gynecology - College of Medicine, Dankook University, Cheonan, Republic of Korea soo8541@hanmail.net.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D045304:Cytochromes c / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D017879:Isothiocyanates; D017382:Reactive Oxygen Species; C037152:isothiocyanic acid; D045304:Cytochromes c; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D020169:Caspases; C473643:sulphoraphene; D002945:Cisplatin
keywords: PI3K; PTEN; Sulforaphene; apoptosis; cisplatin; synergy