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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 894386, 11 pages
http://dx.doi.org/10.1155/2013/894386
Research Article

Inhibitory Effects of PC-SPESII Herbal Extract on Human Breast Cancer Metastasis

Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong, Shanghai 201203, China

Received 13 March 2013; Accepted 28 April 2013

Academic Editor: Yong Qing Yang

Copyright © 2013 Xiu-Feng Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cancer metastasis is refractory to most forms of chemotherapy. Conventional and alternative drugs, such as Chinese herbal remedies, have been developed to target metastatic cancer cells. In this study, we investigated the effects of PC-SPESII, an herbal formulation, on the migration, invasion, and metastasis of an experimental human breast cancer cell line in vivo and in vitro. PC-SPESII suppressed pulmonary metastasis and tumor growth of MDA-MB-231 human breast cancer xenografts without affecting body weight, liver function, and kidney function. PC-SPESII also inhibited MDA-MB-231 cell migration and invasion in vitro in a dose-dependent manner. Based on ELISA analysis, secretion of MMP-2 and MMP-9, proteins associated with extracellular matrix degradation, was reduced in response to PC-SPESII treatment. Western blot analysis of whole-cell extracts revealed that the levels of proteolytic proteins associated with matrix and base membrane degradation (MMP-2, MMP-9, and uPA) were decreased and the levels of their endogenous inhibitors (TIMP1 and TIMP2) were increased. Moreover, the p38MAPK and SAPK/JNK signaling pathway, which stimulates proteolytic enzymes and matrix degradation, was inhibited by PC-PSESII. Remarkably, cotreatment with PC-PSESII and p38MAPK or SAPK/JNK inhibitors magnified the antimetastatic phenotype. Our results indicate that PC-PSESII impairs human breast cancer metastasis by regulating proteolytic enzymes and matrix dynamics through the p38MAPK and SAPK/JNK pathway.