title: SH003 enhances paclitaxel chemosensitivity in MCF-7/PAX breast cancer cells through inhibition of MDR1 activity.
abstract: Paclitaxel is an anti-cancer drug for treating cancer, but paclitaxel resistance is reported in cancer cells. Multidrug resistance (MDR) is related with the epithelial-to-mesenchymal transition (EMT) mechanism, which plays a key role in cancer metastasis. Moreover, EMT mechanism is connected to tamoxifen resistance in breast cancer cells. Consequently, oncologists are interested in finding new MDR1 inhibitors originating from herbal medicines to have less side-effect. Here, we investigated an inhibition effect of SH003 on MDR1 activity in paclitaxel-resistant MCF-7/PAX breast cancer cells. Our results showed that paclitaxel did not inhibit a proliferation in paclitaxel-resistant MCF-7 breast cancer cells. Paclitaxel-resistant MCF-7 cells showed an increase of MDR1 activity, which was confirmed by measuring an amount of accumulated rhodamine 123 in the cells. Also, qRT-PCR and Western blot assays confirmed that paclitaxel-resistant MCF-7 cells exhibited high MDR1 expression level. Furthermore, paclitaxel-resistant MCF-7 cells showed mesenchymal morphology with alterations of EMT markers, and acquired tamoxifen resistance with a decrease of ERα expression. We also found that a combinatorial treatment of SH003 and paclitaxel in paclitaxel-resistant MCF-7 cells caused apoptosis in synergistic manner, which was due to SH003 inhibition of MDR1 expression. Therefore, SH003 could be a potential agent for overcoming MDR in drug-resistant cancer cells.
authors.affiliation: Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
authors.forename: Hyeong Sim
authors.initials: HS
authors.lastname: Choi
authors.affiliation: Department of Biotechnology, Korea National University of Transportation, 61 University Rd., Jeungpyeong, Chungbuk, 368-701, Korea.
authors.forename: Sung-Gook
authors.initials: SG
authors.lastname: Cho
authors.affiliation: Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Science in Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Applied Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Jang
authors.affiliation: Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul, 130-701, Korea. epiko@khu.ac.kr.
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Ko
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism; D029969:Angelica; D027883:Astragalus Plant; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D029778:Trichosanthes
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D009363:Neoplasm Proteins; D010936:Plant Extracts; C000613735:SH003 extract; D017239:Paclitaxel
keywords: Apoptosis; EMT; MDR1; Paclitaxel-resistant breast cancer; SH003