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Plumbagin Enhances Tamoxifen Sensitivity and Inhibits Tumor Invasion in Endocrine Resistant Breast Cancer through EMT Regulation
Author(s) -
Sakunrangsit Nithidol,
Kalpongnukul Nuttiya,
Pisitkun Trairak,
Ketchart Wannarasmi
Publication year - 2016
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5702
Subject(s) - plumbagin , breast cancer , tamoxifen , metastasis , cancer research , cancer , medicine , epithelial–mesenchymal transition , endocrine system , metastatic breast cancer , oncology , biology , hormone , genetics
Tamoxifen is widely used as the first line drug for estrogen receptor‐positive subtype which is expressed in 70% of overall breast cancer patients. However, approximately 50% of these patients develop acquired resistance after 5 years of treatment, which is characterized by tumor recurrence and metastasis. The epithelial mesenchymal transition (EMT) is an important process in breast cancer invasion. Fundamentally, targeting the EMT represents a crucial therapeutic strategy for preventing or treating breast cancer metastasis. Plumbagin (PLB) is a natural naphthoquinone with significant anticancer effects against several types of tumor cells including breast cancer. In this study, we investigated the effect of PLB on human endocrine‐resistant breast cancer cell growth, invasion and the possible mechanisms underlying such actions. PLB exhibited potent cytotoxic activity at a micromolar concentration against endocrine‐resistant breast cancer cells. Interestingly, a fixed low concentration of PLB and tamoxifen combination resulted in an increase in growth inhibition in endocrine‐resistant cells. In addition, PLB also significantly suppressed mesenchymal biomarker expressions that govern the EMT process, resulting in attenuated metastatic capabilities. In conclusion, PLB should be developed as a pharmacological agent for the use as a single treatment or in combination for endocrine‐resistant breast cancer. Copyright © 2016 John Wiley & Sons, Ltd.