NDLI: Efficacy and mechanism of action of Deguelin in suppressing metastasis of 4T1 cells

Content Provider	Springer Nature Link
Author	Mehta, Rajeshwari R. Katta, Harshadadevi Kalra, Amit Patel, Rutulkumar Gupta, Akash Alimirah, Fatouma Murillo, Geveva Peng, Xinjian Unni, Aditya Muzzio, Miguel Mehta, Rajendra G.
Copyright Year	2013
Abstract	Cancer related deaths in breast cancer patients are due to metastasis of the disease. Murine 4T1 cells (Murine mammary cancer cell line developed from 6-thioguanine resistant tumor) provide an excellent research tool for metastasis related studies because these cells are highly aggressive and readily metastasize to the lungs. In this study we determined the effect of Deguelin on in vivo/vitro growth and metastasis of 4T1 cells. Deguelin inhibited the in vitro growth of 4T1 cells in a time and dose dependent manner accompanied with reduced nuclear PCNA immunostaining. In cells treated with Deguelin, reduced expression of nuclear c-Met, and its downstream targets such p-ERK and p-AKT was observed. Deguelin reduced the cell migration in 4T1 cells as determined by scratch wound assay. Combined treatment with Deguelin + ERK or PI3K/AKT inhibitor had no additional effect on cell migration. These results indicated that the action of Deguelin on cell migration may be mediated by AKT and ERK mediated signaling pathways. In vivo, Deguelin treatment significantly inhibited growth of 4T1 cells. Deguelin also reduced the occurrence of metastatic lung lesions by 33 % when cells were injected intravenously into Balb/c female mice. There was no difference in the body weight, nor was there a difference in liver and spleen weights between vehicle treated-control and Deguelin-treated animals, which indicated that Deguelin was nontoxic at the dose used in the present study. These results provide rationale for developing Deguelin as a chemotherapeutic agent for triple negative breast cancer patients.
Starting Page	855
Ending Page	866
Page Count	12
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	30
Issue Number	7
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-05-05
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	4T1 cells Metastasis Biomarkers Deguelin TNBC Cancer Research Biomedicine general Oncology Hematology Surgical Oncology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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