Vitamin D 3 decreases glycolysis and invasiveness, and increases cellular stiffness in breast cancer cells

Julianna Maria Santos, Zeina Shereen Khan, Maliha Tabassum Munir, Kaiser Tarafdar, Shaikh Mizanoor Rahman, Fazle Hussain

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Breast cancer is one of the major causes of death in the USA. Cancer cells, including breast, have high glycolysis rates to meet their energy demands for survival and growth. Vitamin D 3 (VD 3 ) is important for many important physiological processes such as bone mineralization, but its anticancer role is yet to be proven. We find that VD 3 treatment significantly down-regulates glycolytic enzymes and genes and decreases glucose uptake — for both lowly metastatic MCF-7 and highly metastatic MDA-MB-231 (MB231) breast cancer cells. VD 3 also significantly decreases cell viability by inducing apoptosis — consistent with decreased expression of mammalian target of rapamycin (mTOR), which regulates glycolysis and cancer cell survival, and increases 5′ adenosine monophosphate-activated protein kinase (AMPK) activation. These changes accompany a significant reduction of cell migration and increased cell stiffness, presumably a consequence of reversal of the epithelial to mesenchymal transition resulting in increased E-cadherin, and F-actin, and reduced vimentin expression. High levels of cytoskeletal and cortical F-actin may cause high cell stiffness. VD 3 -induced mechanical changes are stronger in highly metastatic MB231 than in lowly metastatic MCF-7 cells. Our results suggest therapeutic and preventive roles of VD 3 in breast cancer.

Original languageEnglish
Pages (from-to)111-120
Number of pages10
JournalJournal of Nutritional Biochemistry
Volume53
DOIs
StatePublished - Mar 2018

Keywords

  • Breast cancer
  • Cell mechanics
  • Cell migration
  • EMT
  • Glycolytic enzymes
  • Vitamin D

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