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Inhibitory Effects of PC-SPESII Herbal Extract on Human Breast Cancer Metastasis
Xiu-Feng Wang1, Jia Du, Tian-Ling Zhang
1Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong, Shanghai 201203, China.
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.
Insights
PC-SPESII, an herbal formulation, effectively suppresses breast cancer metastasis and tumor growth by inhibiting cell migration and invasion. It targets key proteins and signaling pathways involved in extracellular matrix degradation, offering a promising alternative treatment.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Cancer metastasis remains a significant challenge in chemotherapy.
- Herbal remedies are explored as alternative treatments for metastatic cancer.
- Understanding the molecular mechanisms of metastasis is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the anti-metastatic effects of PC-SPESII on human breast cancer cells.
- To elucidate the molecular pathways targeted by PC-SPESII in inhibiting metastasis.
- To evaluate the safety and efficacy of PC-SPESII in preclinical models.
Main Methods:
- In vivo studies using MDA-MB-231 human breast cancer xenografts.
- In vitro assays for cell migration and invasion.
- ELISA and Western blot analysis to assess protein expression levels.
- Investigated the role of p38MAPK and SAPK/JNK signaling pathways.
Main Results:
- PC-SPESII suppressed pulmonary metastasis and tumor growth without adverse effects on body weight or organ function.
- PC-SPESII inhibited MDA-MB-231 cell migration and invasion in a dose-dependent manner.
- PC-SPESII reduced the secretion and levels of matrix metalloproteinases (MMP-2, MMP-9) and urokinase plasminogen activator (uPA), while increasing their inhibitors (TIMP1, TIMP2).
- PC-SPESII inhibited the p38MAPK and SAPK/JNK signaling pathways, and co-treatment with pathway inhibitors enhanced the anti-metastatic effect.
Conclusions:
- PC-SPESII demonstrates significant anti-metastatic properties against human breast cancer.
- The mechanism involves the regulation of proteolytic enzymes and matrix dynamics via the p38MAPK and SAPK/JNK pathways.
- PC-SPESII holds potential as a therapeutic agent for managing breast cancer metastasis.
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