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.