Safflower Yellow Prevents Pulmonary Metastasis of Breast Cancer by Inhibiting Tumor Cell Invadopodia.

Abstract

Carthamus tinctorius L. is a traditional Chinese medicine that activates blood circulation and dissipates blood stasis, and has been extensively used as antitumor treatment in a clinical setting in single or in compound preparation form. However, empirical evidence and a better understanding of the possible mechanisms involved are still required. Here, we investigated the role of safflower yellow (SY), the active ingredient of C. tinctorius, in the pulmonary metastasis of breast cancer, and the underlying mechanism of action. EGF-meditated time- and dose-dependent cell response profiles were applied to screen for the activity of SY in vitro, while orthotopic lung metastasis and intravenous injection were used to evaluate the antimetastatic role of SY in vivo. SY could dose-dependently inhibit EGF-mediated time- and dose-dependent cell response profiles by inhibiting cytoskeletal rearrangement. We also found that SY significantly inhibited the migration of breast cancer cells in vitro and pulmonary metastasis of breast cancer cells in vivo. Consistent with these phenotypes, formation of invadopodia and the expression of MMP-9 and p-Src proteins were decreased after EGF stimulation in MBA-MD-231 cells treat with SY, as well as in lung metastatic foci. Additionally, circulating tumor cells retained in lung capillaries were also reduced. These results suggest that the antimetastatic effect of SY is due to its inhibition of invadopodia formation, which occurs mainly through Src-dependent cytoskeleton rearrangement. We suggest that SY should be considered as a potential novel therapeutic agent for the treatment of breast cancer.

• Authors: Huiying Fu, Renjie Wu, Yuanyuan Li, Lizong Zhang, Xiaofang Tang, Jue Tu, Weimin Zhou, Jianchao Wang, Qiyang Shou
• Journal: The American journal of Chinese medicine (Am J Chin Med) Vol. 44 Issue 7 Pg. 1491-1506 ( 2016) ISSN: 1793-6853 [Electronic] Singapore
• PMID: 27776431 (Publication Type: Journal Article)

Chemical References

• safflower yellow
• Chalcone
• Epidermal Growth Factor
• Proto-Oncogene Proteins pp60(c-src)
• Matrix Metalloproteinase 9

Topics

• Animals
• Breast Neoplasms (pathology)
• COS Cells
• Carthamus tinctorius (chemistry)
• Chalcone (analogs & derivatives, isolation & purification, pharmacology, therapeutic use)
• Chlorocebus aethiops
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Epidermal Growth Factor
• Female
• Humans
• Lung Neoplasms (metabolism, pathology, prevention & control, secondary)
• MCF-7 Cells
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Mice, Inbred BALB C
• Phytotherapy
• Podosomes (drug effects)
• Proto-Oncogene Proteins pp60(c-src) (metabolism)