title: Discovery of lesser known flavones as inhibitors of NF-κB signaling in MDA-MB-231 breast cancer cells--A SAR study.
abstract: Seventeen flavonoids with different substitutions were evaluated for inhibition of nuclear factor-κB (NF-κB) signaling in the invasive breast cancer cell line MDA-MB-231. They were screened using an engineered MDA-MB-231 cell line reporting NF-κB activation. The modulation of expression of two NF-κB regulated genes involved in tumorigenesis, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase-2 (COX-2) were also analyzed in these cells. Among the compounds tested, all except gossypetin and quercetagetin inhibited the activation of NF-κB, and the expression of MMP-9 and COX-2 to different degree. Methylated flavone, chrysoeriol (luteolin-3'-methylether), was found to be the most potent inhibitor of MMP-9 and COX-2 expressions. The effect of chrysoeriol on cell proliferation, cell cycle, apoptosis and metastasis was analyzed by established methods. Chrysoeriol caused cell cycle arrest at G2/M and inhibited migration and invasion of MDA-MB-231 cells. The structure-activity relations amongst the flavonoids as NF-κB signaling inhibitors was studied. The study indicates differences between the actions of various flavonoids on NF-κB activation and on the biological activities of breast cancer cells. Flavones in general, were more active than the corresponding flavonols.
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri Campus, Clappana P.O., Kollam 690 525, Kerala, India.
authors.forename: K
authors.initials: K
authors.lastname: Amrutha
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri Campus, Clappana P.O., Kollam 690 525, Kerala, India.
authors.forename: Pandurangan
authors.initials: P
authors.lastname: Nanjan
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri Campus, Clappana P.O., Kollam 690 525, Kerala, India.
authors.forename: Sanu K
authors.initials: SK
authors.lastname: Shaji
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri Campus, Clappana P.O., Kollam 690 525, Kerala, India.
authors.forename: Damu
authors.initials: D
authors.lastname: Sunilkumar
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri Campus, Clappana P.O., Kollam 690 525, Kerala, India.
authors.forename: K
authors.initials: K
authors.lastname: Subhalakshmi
authors.affiliation: Anthem Biosciences, No. 49, Canara Bank Road, Bommasandra Industrial Area, Phase 1, Hosur Road, Bangalore 560 099, Karnataka, India.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rajakrishna
authors.affiliation: Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri Campus, Clappana P.O., Kollam 690 525, Kerala, India.
authors.forename: Asoke
authors.initials: A
authors.lastname: Banerji
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D047309:Flavones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D047309:Flavones; D016328:NF-kappa B
keywords: Breast cancer; COX-2; Chrysoeriol; Metastasis; Methylated flavonoids; NF-κB