Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1
Authors Li S, Yan T, Deng R, Jiang X, Xiong H, Wang Y, Yu Q, Wang X, Chen C, Zhu Y
Received 2 May 2017
Accepted for publication 16 August 2017
Published 3 October 2017 Volume 2017:10 Pages 4809—4819
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 2
Editor who approved publication: Dr Carlos Vigil Gonzales
Shoushan Li,1,* Ting Yan,2,* Rong Deng,3,* Xuesong Jiang,4 Huaping Xiong,1 Yuan Wang,1 Qiao Yu,3 Xiaohua Wang,5 Cheng Chen,4 Yichao Zhu6,7
1Department of Oncology, Traditional Chinese Medical Hospital of Siyang County, 2Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, 3Department of General Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, 4Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, 5Department of Chemotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, 6Department of Physiology, Nanjing Medical University, 7State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
*These authors contributed equally to this work
Purpose: Triple-negative breast cancer (TNBC) is an especially aggressive and hard-to-treat disease. Although the anticancer role of kaempferol has been reported in breast cancer, the effect of kaempferol on TNBC remains unclear.
Materials and methods: This experiment investigated the migration-suppressive role of a low dose of kaempferol in TNBC cells. Wound-healing assays and cell invasion assays were used to confirm the migration and invasion of cells treated with kaempferol or transfected indicated constructs. We evaluated the activations of RhoA, Rac1 and Cdc42 in TNBC cells with a Rho activation assay. A panel of inhibitors of estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 (ER/PR/HER2) treated non-TNBC (SK-BR-3 and MCF-7) cells and blocked the ER/PR/HER2 activity. Wound-healing assays and Rho activation assays were employed to measure the effect of kaempferol and ER/PR/HER2 inhibitors on Rho activation and cell migration rates.
Results: A low dose of kaempferol (20 µmol/L) had a potent inhibitory effect on the migration and invasion of TNBC cells, but not on the migration of non-TNBC (SK-BR-3 and MCF-7) cells. The low dose of kaempferol downregulated the activations of RhoA and Rac1 in TNBC cells. Moreover, the low dose of kaempferol also inhibited the migration and RhoA activations of HER2-silence SK-BR-3 and ER/PR-silence MCF-7 cells. Overexpressed HER2 rescued the cell migration and RhoA and Rac1 activations of kaempferol-treated MDA-MB-231 cells.
Conclusion: The low dose of kaempferol inhibits the migration and invasion of TNBC cells via blocking RhoA and Rac1 signaling pathway.
Keywords: kaempferol, TNBC, migration, invasion, RhoA, Rac1
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