title: Ellagic acid exerts anti-proliferation effects via modulation of Tgf-β/Smad3 signaling in MCF-7 breast cancer cells.
abstract: Ellagic acid has been shown to inhibit tumor cell growth. However, the underlying molecular mechanisms remain elusive. In this study, our aim was to investigate whether ellagic acid inhibits the proliferation of MCF- 7 human breast cancer cells via regulation of the TGF-β/Smad3 signaling pathway. MCF-7 breast cancer cells were transfected with pEGFP-C3 or pEGFP-C3/Smad3 plasmids, and treated with ellagic acid alone or in combination with SIS3, a specific inhibitor of Smad3 phosphorylation. Cell proliferation was assessed by MTT assay and the cell cycle was detected by flow cytometry. Moreover, gene expression was detected by RT-PCR, real-time PCR and Western blot analysis. The MTT assay showed that SIS3 attenuated the inhibitory activity of ellagic acid on the proliferation of MCF-7 cells. Flow cytometry revealed that ellagic acid induced G0/G1 cell cycle arrest which was mitigated by SIS3. Moreover, SIS3 reversed the effects of ellagic acid on the expression of downstream targets of the TGF-β/Smad3 pathway. In conclusion, ellagic acid leads to decreased phosphorylation of RB proteins mainly through modulation of the TGF-β/Smad3 pathway, and thereby inhibits the proliferation of MCF-7 breast cancer cells.
authors: The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China E-mail : mliu35@aliyun.com, yalan9999@sohu.com.
authors: Tao
authors: T
authors: Zhang
authors: Hong-Sheng
authors: HS
authors: Chen
authors: Li-Feng
authors: LF
authors: Wang
authors: Ming-Han
authors: MH
authors: Bai
authors: Yi-Chong
authors: YC
authors: Wang
authors: Xiao-Feng
authors: XF
authors: Jiang
authors: Ming
authors: M
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004610:Ellagic Acid / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D061986:MCF-7 Cells; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C508504:6,7-dimethyl-2-(2E)-3-(1-methyl-2-phenyl-1H-pyrrolo(2,3-b)pyridin-3-yl-prop-2-enoyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride; D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007546:Isoquinolines; D011725:Pyridines; D011758:Pyrroles; D016160:Retinoblastoma Protein; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D004610:Ellagic Acid