title: Identification of a novel Calotropis procera protein that can suppress tumor growth in breast cancer through the suppression of NF-κB pathway.
abstract: Breast cancer is the most common cancer among women. To date, improvements in hormonal and cytotoxic therapies have not yet led to a sustained remission or cure. In the present study, we investigated the in vitro and in vivo antitumor activities of a novel Calotropis procera protein (CP-P) isolated from root bark. CP-P protein inhibited the proliferation and induced apoptosis of breast cancer cells through the suppression of nuclear factor kappaB (NF-kB) activation. CP-P, when administered individually or in combination with cyclophosphamide (CYC, 0.2 mg/kg) to rats with 7, 12-dimethyl benz(a)anthracene (DMBA)-induced breast cancer decreased tumor volume significantly without affecting the body weight. To elucidate the anticancer mechanism of CP-P, antioxidant activities such as superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and non-enzymatic antioxidant - reduced glutathione (GSH), vitamin E and C generation in the breast were analyzed by various assays. SOD, CAT, GST, GSH, vitamin E and C levels were high in combination-treated groups (CP-P+CYC) versus the CYC alone-treated groups. Also, the combination was more effective in down-regulating the expression of NF-kB-regulated gene products (cyclin D1 and Bcl-2) in breast tumor tissues. Our findings indicate that CP-P possesses significant antitumor activity comparable to a commonly used anticancer drug, cyclophosphamide, and may form the basis of a novel therapy for breast cancer.
authors.affiliation: Infectious Diseases Programme, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, Singapore. rperumalsamy@yahoo.co.uk
authors.forename: Ramar Perumal
authors.initials: RP
authors.lastname: Samy
authors.forename: Peramaiyan
authors.initials: P
authors.lastname: Rajendran
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Narayana Moorthy
authors.initials: NM
authors.lastname: Anandi
authors.forename: Bradley G
authors.initials: BG
authors.lastname: Stiles
authors.forename: Savarimuthu
authors.initials: S
authors.lastname: Ignacimuthu
authors.forename: Gautam
authors.initials: G
authors.lastname: Sethi
authors.forename: Vincent T K
authors.initials: VT
authors.lastname: Chow
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D031107:Calotropis / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010940:Plant Proteins / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D021381:Protein Transport / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D010940:Plant Proteins; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D015127:9,10-Dimethyl-1,2-benzanthracene; D013482:Superoxide Dismutase; D051550:I-kappa B Kinase; D005978:Glutathione; D024502:alpha-Tocopherol