title: Plumbagin Enhances Tamoxifen Sensitivity and Inhibits Tumor Invasion in Endocrine Resistant Breast Cancer through EMT Regulation.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Nithidol
authors.initials: N
authors.lastname: Sakunrangsit
authors.affiliation: Systems Biology Center, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Nuttiya
authors.initials: N
authors.lastname: Kalpongnukul
authors.affiliation: Systems Biology Center, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Trairak
authors.initials: T
authors.lastname: Pisitkun
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
authors.forename: Wannarasmi
authors.initials: W
authors.lastname: Ketchart
mesh_terms: D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D009285:Naphthoquinones / Q000737:chemistry* / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D009285:Naphthoquinones; D013629:Tamoxifen; C014758:plumbagin
keywords: EMT; cytotoxicity; endocrine-resistant breast cancer; metastasis; plumbagin