sch-23390 and Breast-Neoplasms

Existing studies on the mechanism of cell volume regulation are mainly relevant to ion channels and osmosis in extracellular fluid. Recently, accumulating evidence has shown that cellular mechanical microenvironment also influences the cell volume. Herein, we investigated the regulation of substrate stiffness on the cell volume homeostasis of MCF-7 cells and their following migration behaviors. We found that cell volume increases with increasing substrate stiffness, which could be affected by blocking the cell membrane anion permeability and dopamine receptor. In addition, the cell migration is significantly inhibited by decreasing the cell volume using tamoxifen and such inhibition effect on migration is enhanced by increasing substrate stiffness. The cell membrane anion permeability might be the linker between cellular mechanical microenvironment and cellular volume homeostasis regulation. This work revealed the regulation of substrate stiffness on cell volume homeostasis for the first time, which would provide a new perspective into the understanding of cancer metastasis and a promising anti-cancer therapy through regulation of cell volume homeostasis.

Topics: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Acrylic Resins; Anion Transport Proteins; Antineoplastic Agents, Hormonal; Benzazepines; Breast Neoplasms; Cell Adhesion; Cell Membrane; Cell Membrane Permeability; Cell Movement; Cell Size; Collagen; Female; Humans; Hydrogels; Hypotonic Solutions; MCF-7 Cells; Osmoregulation; Porosity; Receptors, Dopamine D1; Tamoxifen; Tumor Microenvironment

A high-throughput screen (HTS) was conducted against stably propagated cancer stem cell (CSC)-enriched populations using a library of 300,718 compounds from the National Institutes of Health (NIH) Molecular Libraries Small Molecule Repository (MLSMR). A cinnamide analog displayed greater than 20-fold selective inhibition of the breast CSC-like cell line (HMLE_sh_Ecad) over the isogenic control cell line (HMLE_sh_eGFP). Herein, we report structure-activity relationships of this class of cinnamides for selective lethality towards CSC-enriched populations.

Topics: Amides; Breast Neoplasms; Cell Line, Tumor; Drug Screening Assays, Antitumor; Female; Humans; Neoplastic Stem Cells; Small Molecule Libraries; Structure-Activity Relationship