title: Quercetin regulates β-catenin signaling and reduces the migration of triple negative breast cancer.
abstract: Triple negative breast cancer (TNBC) is characterized by a lack in estrogen, progesterone, and epidermal growth factor 2 receptors. TNBC exhibits most of the characteristics of basal-like and claudin-low breast cancer subtypes. The main contributor in the mortality of TNBC is due to the higher invasive and migratory ability of these tumor cells. Some plant flavonoids inhibit the epithelial mesenchymal transition (EMT) of tumor cells and suppress cancer metastasis. In this study, we aimed to determine whether the flavonoid quercetin is effective in modulating the molecular signaling associated with EMT in TNBC. Our data indicated that quercetin can induce the expression of E-cadherin and also downregulate vimentin levels in TNBC. The ability of quercetin to modulate these EMT markers resulted in a mesenchymal-to-epithelial transition (MET). Quercetin-induced MET was linked with the alteration of nuclear localization of β-catenin and modulation of β-catenin target genes such as cyclin D1 and c-Myc. Furthermore, we observed that quercetin induced the anti-tumor activity of doxorubicin by inhibiting the migratory ability of TNBC cells. These results suggested that quercetin may inhibit TNBC metastasis and also improve the therapeutic efficacy of existing chemotherapeutic drugs.
authors.affiliation: Department of Pharmaceutical Sciences, Jefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Asha
authors.initials: A
authors.lastname: Srinivasan
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Chellappagounder
authors.initials: C
authors.lastname: Thangavel
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences, Jefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Sunday
authors.initials: S
authors.lastname: Shoyele
authors.affiliation: Department of Radiation Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Den
authors.affiliation: Department of Pharmaceutical Sciences, Jefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Ponniah
authors.initials: P
authors.lastname: Selvakumar
authors.affiliation: Department of Pharmaceutical Sciences, Jefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Ashakumary
authors.initials: A
authors.lastname: Lakshmikuttyamma
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C495270:CTNNB1 protein, human; D051176:beta Catenin; D004317:Doxorubicin; D011794:Quercetin
keywords: EMT markers; Triple negative breast cancer; drug resistance; flavonoids