ABSTRACT:
Flavonoids are naturally occurring polyphenolic compounds present in fruits, bark, stem, wine, tea etc. These plant secondary metabolites exhibit wide range of activities such as antioxidant, anti-antibacterial, anticancer, anti-inflammatory, anti-hyperglycemicetc. Most of these flavonoids are classified as endocrine disruptor, estrogen mimicker or as antioxidants without estrogenic effect. The primary objective of this study was to assess the estrogenic activity of karanjin, a bioactive furanoflavonoidindigenous toPongamiapinnata, on ER-alphapositiveMCF-7 breast cancer cell line. Using cell viability assay,it was found that I pM karanjin increased cell viability by 1.4 fold in MCF-7 cells. Additionally, karanjin does not affect viability of ER-alpha negative MDA-MB-231 cells suggesting effect of karanjin on MCF-7 cells to be ER-alpha dependent. Furthermore, gene expression profiling of three known estrogen responsive genes CSTA, ADAMSTS19 and pS2 was done byquantitative real time RT- PCR.In line with E2, mRNA expression of CSTA and ADAMSTS 19 gene was down- regulated and pS2 gene was up-regulated when MCF-7 cells were treated with 1 pM karanjin for 24 h. Moreover, immunocytochemical studies have shown that ER-alpha protein in karanjin-treated MCF-7 cells was reduced in the nuclei, an etfect akin to estrogen treated MCF-7 cells. This is the first report with regard to the estrogenic effect of karanjin at physiological relevant concentration indicating its phytoestrogenic property in human breast cancer.
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