title: Genistein synergizes centchroman action in human breast cancer cells.
abstract: OBJECTIVE
  Despite the progress in the diagnosis and treatment of breast cancer, it remains a major health problem in women. Natural flavones along with chemotherapeutic agents enhance therapeutic response and minimize toxicity of chemical agents. Centchroman (CC) colloquially called as ormeloxifene, is a nonsteroidal oral contraceptive categorized as selective estrogen receptor modulator with anti-breast cancer activity. Genistein (GN), an isoflavone found mainly in soy products possesses anti-cancerous potential against a number of cancers including breast. The present study aims at investigating the combination of CC and GN in human breast cancer cell lines (HBCCs).
  
  
  METHODS
  Cytotoxic effect of CC and GN separately and in combination were assessed by sulforhodamine B (SRB) assay in MDA MB-231, MDA MB-468, MCF-7, T-47D HBCCs, and nontumorigenic human mammary epithelial cell (HMEC) MCF-10A. The drug interaction was analyzed using CompuSyn software through which combination index and dose reduction index were generated.
  
  
  RESULTS
  Combination of CC plus GN exerts significantly higher cytotoxicity compared to each drugper sein HBCCs, whereas HMEC-MCF-10A remains unaffected.
  
  
  CONCLUSIONS
  On an overall basis, the drugs in combination enhanced cell killing in malignant cells. Therefore, the combination of CC with GN may offer a novel approach for the breast cancer.
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Taramani, Chennai, Tamil Nadu, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Kaushik
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India; Centre for Advance Research, King George's Medical University, Lucknow, Uttar Pradesh, India.
authors.forename: Hari
authors.initials: H
authors.lastname: Shyam
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Taramani, Chennai, Tamil Nadu, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Balapure
mesh_terms: D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002486:Centchroman / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004965:Estrogen Antagonists / Q000008:administration & dosage*; D005260:Female; D019833:Genistein / Q000008:administration & dosage*; D006131:Growth Inhibitors / Q000008:administration & dosage; D006801:Humans; D061986:MCF-7 Cells
chemical_list: D016588:Anticarcinogenic Agents; D004965:Estrogen Antagonists; D006131:Growth Inhibitors; D002486:Centchroman; D019833:Genistein
keywords: Centchroman; combination index; dose reduction index; genistein; synergism