title: 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: * Center Laboratory, Second Clinical Medical College, P.R. China.
authors: Huiying
authors: H
authors: Fu
authors: ‡ Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, P.R. China.
authors: Renjie
authors: R
authors: Wu
authors: † Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, P.R. China.
authors: Yuanyuan
authors: Y
authors: Li
authors: † Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, P.R. China.
authors: Lizong
authors: L
authors: Zhang
authors: § Zhejiang Hospital, Hangzhou 310013, P.R. China.
authors: Xiaofang
authors: X
authors: Tang
authors: † Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, P.R. China.
authors: Jue
authors: J
authors: Tu
authors: † Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, P.R. China.
authors: Weimin
authors: W
authors: Zhou
authors: * Center Laboratory, Second Clinical Medical College, P.R. China.
authors: Jianchao
authors: J
authors: Wang
authors: † Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, P.R. China.
authors: Qiyang
authors: Q
authors: Shou
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D019556:COS Cells; D031187:Carthamus tinctorius / Q000737:chemistry*; D002599:Chalcone / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008517:Phytotherapy; D000069261:Podosomes / Q000187:drug effects*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism
chemical_list: C076422:safflower yellow; D002599:Chalcone; D004815:Epidermal Growth Factor; D016392:Proto-Oncogene Proteins pp60(c-src); D020780:Matrix Metalloproteinase 9
keywords: Breast Cancer Metastasis; EGF-Mediated Time- and Dose-Dependent Cell Response Profiles; Invadopodia; Safflower Yellow; p-Src