title: Sulforaphane inhibits growth of human breast cancer cells and augments the therapeutic index of the chemotherapeutic drug, gemcitabine.
abstract: Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking or reversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer related death. One such promising chemopreventive agent which has attracted considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. The present study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent, gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the results by nuclear morphological examination. Further we analyzed the modulation of expression of Bcl-2 and COX-2 on treatment of these cells with SFN by RT-PCR. SFN showed cytotoxic effects on MCF-7 cells in a dose- and time-dependent manner via an apoptotic mode of cell death. In addition, a combinational treatment of SFN and gemcitabine on MCF-7 cells resulted in growth inhibition in a synergistic manner with a combination index (CI) <1. Notably, SFN was found to significantly downregulate the expression of Bcl-2, an anti-apoptotic gene, and COX-2, a gene involved in inflammation, in a time-dependent manner. These results indicate that SFN induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 and COX-2 respectively. The combination of SFN and gemcitabine may potentiate the efficacy of gemcitabine and minimize the toxicity to normal cells. Taken together, SFN may be a potent anti-cancer agent for breast cancer treatment.
authors.affiliation: Department of Biotechnology, Manipal University, Dubai, United Arab Emirates E-mail : chhaviaiims@gmail.com.
authors.forename: Arif
authors.initials: A
authors.lastname: Hussain
authors.forename: Javeria
authors.initials: J
authors.lastname: Mohsin
authors.forename: Sathyen Alwin
authors.initials: SA
authors.lastname: Prabhu
authors.forename: Salema
authors.initials: S
authors.lastname: Begum
authors.forename: Qurrat El-Ain
authors.initials: Qel-A
authors.lastname: Nusri
authors.forename: Geetganga
authors.initials: G
authors.lastname: Harish
authors.forename: Elham
authors.initials: E
authors.lastname: Javed
authors.forename: Munawwar Ali
authors.initials: MA
authors.lastname: Khan
authors.forename: Chhavi
authors.initials: C
authors.lastname: Sharma
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D061986:MCF-7 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013454:Sulfoxides; D000093542:Gemcitabine
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D017879:Isothiocyanates; D019253:Proto-Oncogene Proteins c-bcl-2; D013454:Sulfoxides; D003841:Deoxycytidine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C016766:sulforaphane; D000093542:Gemcitabine