PMID- 29216499 OWN - NLM STAT- MEDLINE DCOM- 20190925 LR - 20211204 IS - 1873-4847 (Electronic) IS - 0955-2863 (Linking) VI - 53 DP - 2018 Mar TI - Vitamin D(3) decreases glycolysis and invasiveness, and increases cellular stiffness in breast cancer cells. PG - 111-120 LID - S0955-2863(17)30358-3 [pii] LID - 10.1016/j.jnutbio.2017.10.013 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Santos, Julianna Maria AU - Santos JM AD - Texas Tech University, Mechanical Engineering Department, Lubbock, TX, USA. FAU - Khan, Zeina Shereen AU - Khan ZS AD - Texas Tech University, Mechanical Engineering Department, Lubbock, TX, USA. FAU - Munir, Maliha Tabassum AU - Munir MT AD - Texas Tech University, Nutritional Sciences, Lubbock, TX, USA. FAU - Tarafdar, Kaiser AU - Tarafdar K AD - Covenant Medical Center, Lubbock, TX, USA. FAU - Rahman, Shaikh Mizanoor AU - Rahman SM AD - Texas Tech University, Nutritional Sciences, Lubbock, TX, USA. Electronic address: shaikh.rahman@ttu.edu. FAU - Hussain, Fazle AU - Hussain F AD - Texas Tech University, Mechanical Engineering Department, Lubbock, TX, USA. Electronic address: fazlehussain@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171102 PL - United States TA - J Nutr Biochem JT - The Journal of nutritional biochemistry JID - 9010081 RN - 0 (Enzymes) RN - 1C6V77QF41 (Cholecalciferol) RN - 33X04XA5AT (Lactic Acid) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Apoptosis/drug effects MH - Breast Neoplasms/*drug therapy/metabolism/*pathology MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cell Survival/drug effects MH - Cholecalciferol/*pharmacology MH - Enzymes/genetics/metabolism MH - Epithelial-Mesenchymal Transition/drug effects MH - Female MH - Gene Expression Regulation, Neoplastic/drug effects MH - Glucose/pharmacokinetics MH - Glycolysis/*drug effects/physiology MH - Humans MH - Lactic Acid/metabolism MH - MCF-7 Cells MH - TOR Serine-Threonine Kinases/metabolism OTO - NOTNLM OT - Breast cancer OT - Cell mechanics OT - Cell migration OT - EMT OT - Glycolytic enzymes OT - Vitamin D(3) EDAT- 2017/12/08 06:00 MHDA- 2019/09/26 06:00 CRDT- 2017/12/08 06:00 PHST- 2017/04/21 00:00 [received] PHST- 2017/09/01 00:00 [revised] PHST- 2017/10/18 00:00 [accepted] PHST- 2017/12/08 06:00 [pubmed] PHST- 2019/09/26 06:00 [medline] PHST- 2017/12/08 06:00 [entrez] AID - S0955-2863(17)30358-3 [pii] AID - 10.1016/j.jnutbio.2017.10.013 [doi] PST - ppublish SO - J Nutr Biochem. 2018 Mar;53:111-120. doi: 10.1016/j.jnutbio.2017.10.013. Epub 2017 Nov 2.