title: Phytochemicals potently inhibit migration of metastatic breast cancer cells.
abstract: Cell migration is a major process that drives metastatic progression of cancers, the major cause of cancer death. Existing chemotherapeutic drugs have limited efficacy to prevent and/or treat metastasis, emphasizing the need for new treatments. We focus on triple negative breast cancer (TNBC), the subtype of breast cancer with worst prognosis and no standard chemotherapy protocols. Here we demonstrate that a group of natural compounds, known as phytochemicals, effectively block migration of metastatic TNBC cells. Using a novel cell micropatterning technology, we generate consistent migration niches in standard 96-well plates where each well contains a cell-excluded gap within a uniform monolayer of cells. Over time, cells migrate into and occupy the gap. Treating TNBC cells with non-toxic concentrations of phytochemicals significantly blocks motility of cells. Using a molecular analysis approach, we show that anti-migratory property of phytochemicals is partly due to their inhibitory effects on phosphorylation of ERK1/2. This study provides a framework for future studies to understand molecular targets of phytochemicals and evaluate their effectiveness in inhibiting metastasis in animal models of cancer.
authors.affiliation: Department of Biomedical Engineering, The University of Akron, Akron, Ohio 44325, USA. tavana@uakron.edu.
authors.forename: Stephanie Lemmo
authors.initials: SL
authors.lastname: Ham
authors.forename: Samila
authors.initials: S
authors.lastname: Nasrollahi
authors.forename: Kush N
authors.initials: KN
authors.lastname: Shah
authors.forename: Andrew
authors.initials: A
authors.lastname: Soltisz
authors.forename: Sailaja
authors.initials: S
authors.lastname: Paruchuri
authors.forename: Yang H
authors.initials: YH
authors.lastname: Yun
authors.forename: Gary D
authors.initials: GD
authors.lastname: Luker
authors.forename: Anupam
authors.initials: A
authors.lastname: Bishayee
authors.forename: Hossein
authors.initials: H
authors.lastname: Tavana
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D017022:Flow Injection Analysis / Q000379:methods; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D064209:Phytochemicals / Q000008:administration & dosage*; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*
chemical_list: D000970:Antineoplastic Agents; D064209:Phytochemicals