Astaxanthin Decreases Invasion and MMP Activity in Triple Negative Breast Cancer Cells

Astaxanthin is a non-vitamin A carotenoid that has gained wide acceptance as a dietary supplement. We investigated whether Astaxanthin was effective against invasion and metastasis of triple-negative breast cancer (TNBC) cells. We determined that Astaxanthin decreases invasion of 4T1 cells through Matrigel^TM, but does not affect proliferation. Using zymography we showed that 4T1 cells treated with Astaxanthin demonstrate decreased MMP-2, -9, and -13 activities. Western blot analysis of conditioned media and lysates suggests that decreased MMP activity results from decreased protein expression. Using a broad-spectrum MMP inhibitor we observed a decrease in invasion of 4T1 cells similar to the decrease seen with Astaxanthin treatment, suggesting that invasion of 4T1 cells is at least partially MMP dependent and that Astaxanthin may inhibit invasion via downregulation of MMP activity. Using an RTK array to identify signaling pathways altered by Astaxanthin in 4T1 cells, we found decreased constitutive phosphorylation of AKT and STAT3, both of which have been implicated in regulation of MMP expression and invasion. Treatment of 4T1 cells with STAT3 inhibitor decreased invasion, inhibited STAT3 phosphorylation, and decreased MMP-9 expression. Using the 4T1 model of spontaneous metastases, we determined that an Astaxanthin-rich diet significantly decreased tumor weight and volume, and decreased incidence of metastasis and metastatic burden. Taken together, our data suggest that Astaxanthin decreases invasion and metastasis through modulation of AKT, STAT3, and MMP activity.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2012

Author dc:creator

• Stadelman, Kristin Marie

• Astaxanthin

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/37425

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/37425