title: Curcumin suppresses 4-hydroxytamoxifen resistance in breast cancer cells by targeting SLUG/Hexokinase 2 pathway.
abstract: Triple negative breast cancer (TNBC) is the hardest breast cancer subtype to treat due to lacking therapeutic target and treatment options. In this study, we found that SLUG expression was much higher in TNBC MDA-MB-231 cells than estrogen receptor alpha (ERα) positive breast cancer MCF7 cells. 4-hydroxytamoxifen (4-OHT) promoted SLUG expression, which was blocked by curcumin. Further investigation showed that SLUG activated the transcription of hexokinase-2 (HK2) by binding to HK2 promoter. SLUG knockdown inhibited HK2 expression and weakened 4-OHT resistance of MDA-MB-231 cells. Conversely, SLUG overexpression elevated HK2 level and increased 4-OHT resistance of MCF7 cells. Combination of curcumin and 4-OHT suppressed SLUG and HK2 expression, leading to mitochondrion-mediated apoptosis. These results suggested SLUG as a potential target and curcumin as a promising natural agent for overcoming 4-OHT resistance of TNBC.
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China.
authors.forename: Chong
authors.initials: C
authors.lastname: Geng
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China.
authors.forename: Jiyu
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China; Department of General Surgery, Jinan Hospital, Jinan 250013, Shandong, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China.
authors.forename: Zhun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Dong
authors.affiliation: Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, PR China. Electronic address: txs0509@sina.cn.
authors.forename: Xingsong
authors.initials: X
authors.lastname: Tian
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D047369:Chromatin Immunoprecipitation; D003474:Curcumin / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D000071250:Snail Family Transcription Factors; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000737:chemistry; D014157:Transcription Factors / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D013629:Tamoxifen; C016601:afimoxifene; C000609700:HK2 protein, human; D006593:Hexokinase; D003474:Curcumin
keywords: 4-Hydroxytamoxifen; Breast cancer; Curcumin; Hexokinase-2; SLUG