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Low Dose of Acacetin Promotes Breast Cancer MCF-7 Cells Proliferation Through the Activation of ERK/ PI3K /AKT and Cyclin Signaling Pathway

[ Vol. 13 , Issue. 3 ]

Author(s):

Huanhuan Ren, Jun Ma, Lingling Si, Boxue Ren, Xiaoyu Chen, Dan Wang, Wenjin Hao, Xuexi Tang, Defang Li* and Qiusheng Zheng*   Pages 368 - 377 ( 10 )

Abstract:


Background: Phytoestrogens have been proposed as replaceable medicines for climacteric hormone replacement therapy, on the basis of EP3138562 and US5516528. However, recent studies demonstrated that phytoestrogens might promote the proliferation of breast cancer cells, which is rooted in their estrogenic activity. Acacetin, as one phytoestrogen, has been reported to exhibit estrogenic activity. But the effect of acacetin on breast cancer cells proliferation and its mechanism has not been explored.

Objective: This study aims to evaluate the effects of acacetin on breast cancer MCF-7 cells proliferation and to explore its possible mechanism.

Methods: Sulforhodamine B (SRB) assay was used to test the proliferation rate of MCF-7 cells. Flow cytometry was utilized to determine cell cycle. RT-qPCR and western blot were employed to evaluate the expressions of proliferation-related factors in mRNA and protein levels.

Results: According to SRB assay and flow cytometric analysis, low dose of acacetin from 10-3 to 1µM promoted the MCF-7 cells proliferation in a dose-dependent and time-dependent manner. Moreover, the expressions of cell cycle-related molecules, ERK1/2 and PI3K/AKT were increased after treatment with acacetin, while the increases were effectively reversed by ER antagonist ICI 182,780. Further studies showed that acacetin notably induced increasing mRNA and proteins levels of ERα, which were strongly reversed by ERα antagonist MPP.

Conclusion: Low dose of acacetin from 10-3 µM to µM promoted the proliferation of MCF-7 cells through the ERK/PI3K/AKT pathway and its downstream cyclin signaling. And ERα is mainly responsible for acacetin promoting proliferation in MCF-7 cells.

Keywords:

Acacetin, breast cancer, MCF-7 cells, mechanism, phytoestrogen, proliferation.

Affiliation:

Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832002, Xinjiang, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832002, Xinjiang, Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832002, Xinjiang, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, Shandong, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003, Shandong, Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832002, Xinjiang



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