title: Activation of the CRABPII/RAR pathway by curcumin induces retinoic acid mediated apoptosis in retinoic acid resistant breast cancer cells.
abstract: Due to the anti-proliferative and anti-apoptotic effects of retinoic acid (RA), this hormone has emerged as a target for several diseases, including cancer. However, development of retinoid resistance is a critical issue and efforts to understand the retinoid signaling pathway may identify useful biomarkers for future clinical trials. Apoptotic responses of RA are exhibited through the cellular RA-binding protein II (CRABPII)/retinoic acid receptor (RAR) signaling cascade. Delivery of RA to RAR by CRABPII enhances the transcriptional activity of genes involved in cell death and cell cycle arrest. The purpose of this study was to investigate the role of curcumin in sensitizing RA-resistant triple-negative breast cancer (TNBC) cells to RA-mediated apoptosis. We provide evidence that curcumin upregulates the expression of CRABPII, RARβ and RARγ in two different TNBC cell lines. Co-treatment of the cells with curcumin and RA results in increased apoptosis as demonstrated by elevated cleavage of poly(ADP-ribose) polymerase and cleaved caspase-9. Additionally, silencing CRABPII reverses curcumin sensitization of TNBC cells to the apoptotic inducing effects of RA. These findings provide mechanistic insights into sensitizing TNBC cells to RA-mediated cell death by curcumin-induced upregulation of the CRABPII/RAR pathway.
authors.affiliation: Department of Biomedical Sciences, College of Allied Health, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Padmamalini
authors.initials: P
authors.lastname: Thulasiraman
authors.affiliation: Department of Biomedical Sciences, College of Allied Health, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Galen
authors.initials: G
authors.lastname: Garriga
authors.affiliation: Department of Biomedical Sciences, College of Allied Health, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Danthuluri
authors.affiliation: Department of Biomedical Sciences, College of Allied Health, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: McAndrews
authors.affiliation: Department of Biomedical Sciences, College of Allied Health, University of South Alabama, Mobile, AL 36688, USA.
authors.forename: Imran Q
authors.initials: IQ
authors.lastname: Mohiuddin
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D018168:Receptors, Retinoic Acid; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin; D003474:Curcumin