title: Liposomes containing (-)-gossypol-enriched cottonseed oil suppress Bcl-2 and Bcl-xL expression in breast cancer cells.
abstract: OBJECTIVE
  We have demonstrated that (-)-gossypol-enriched cottonseed oil [(-)-GPCSO] can down-regulate Bcl-2 expression in MCF-7 and primary cultured human breast cancer epithelial cells (PCHBCECs). However, this agent has not been evaluated in vivo due to its limited solubility. We aimed to develop liposomes containing (-)-GPCSO to suppress Bcl-2/Bcl-xL expression.
  
  
  METHODS
  (-)-GPCSO liposomes were prepared and evaluated for effects on breast cancer cell viability, MDA-MB-231 xenograft tumor growth, cellular Bcl-2 and Bcl-xL mRNA levels, and chemosensitivity to paclitaxel.
  
  
  RESULTS
  (-)-GPCSO liposomes prepared had excellent stability. Cytotoxicity of (-)-GPCSO liposomes was significantly reduced compared to (-)-GPCSO in culture medium. Bcl-2 and Bcl-xL mRNA expression was down-regulated by (-)-GPCSO in culture medium or (-)-GPCSO liposomes in MDA-MB-231 cells. In PCHBCECs, Bcl-2 and Bcl-xL expression were down-regulated by (-)-GPCSO liposomes. (-)-GPCSO in culture medium induced only a mild reduction in Bcl-xL. In the MDA-MB-231 xenograft tumor model, (-)-GPCSO liposomes exhibited tumor-suppressive activity and significantly reduced intratumoral Bcl-2 and Bcl-xL expression. Cytotoxicity of paclitaxel was increased by pretreatment with (-)-GPCSO liposomes in MDA-MB-231 and PCHBCECs.
  
  
  CONCLUSIONS
  Findings suggest that (-)-GPCSO liposomes warrant continued investigation as a chemosensitizer for breast cancers exhibiting Bcl-2-/Bcl-xL-mediated drug resistance.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, Ohio 43210, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Longzhu
authors.initials: L
authors.lastname: Piao
authors.forename: Pingping
authors.initials: P
authors.lastname: Xu
authors.forename: Weiping
authors.initials: W
authors.lastname: Ye
authors.forename: Saiyi
authors.initials: S
authors.lastname: Zhong
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Lin
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Kulp
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Mao
authors.forename: Youngah
authors.initials: Y
authors.lastname: Cho
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.forename: Young C
authors.initials: YC
authors.lastname: Lin
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003369:Cottonseed Oil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006072:Gossypol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein / Q000235:genetics*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003369:Cottonseed Oil; D008081:Liposomes; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D006072:Gossypol; D017239:Paclitaxel