PMID- 29746779
OWN - NLM
STAT- MEDLINE
DCOM- 20190703
LR  - 20190703
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 15
IP  - 6
DP  - 2018 Jun 4
TI  - Energy Metabolism Drugs Block Triple Negative Breast Metastatic Cancer Cell 
      Phenotype.
PG  - 2151-2164
LID - 10.1021/acs.molpharmaceut.8b00015 [doi]
AB  - To establish alternative targeted therapies against triple negative (TN) breast 
      cancer, the energy metabolism and the sensitivity of cell growth, migration, and 
      invasiveness toward metabolic, canonical, and NSAID inhibitors were analyzed in 
      MDA-MB-231 and MDA-MB-468, two TN metastatic breast cancer cell lines, under both 
      normoxia (21% O(2)) and hypoxia (0.1% O(2)). For comparative purposes, the 
      analysis was also carried out in the less-metastatic breast MCF-7 cancer cells. 
      Under normoxia, oxidative phosphorylation (OxPhos) was significantly higher 
      (2-times) in MDA-MB-468 than in MDA-MB-231 and MCF-7, whereas their glycolytic 
      fluxes and OxPhos and glycolytic protein contents were all similar. TN cancer 
      cell lines mainly depended on OxPhos (62-75%), whereas MCF-7 cells equally 
      depended on both pathways for ATP supply. Hypoxia for 24 h promoted a significant 
      increase (>20 times) in the glycolytic transcriptional master factor HIF1-alpha in 
      its target proteins GLUT-1, HKI and II, and LDH-A (2-4 times) as well as in the 
      glycolytic flux (1.3-2 times) vs normoxia in MDA-MB-468, MDA-MB-231, and MCF-7. 
      On the contrary, hypoxia decreased (15-60%) the contents of COXIV, 2OGDH, ND1, 
      and ATP synthase as well as the OxPhos flux (50-75%), correlating with a high 
      mitophagy level in the three cell lines. Under hypoxia, the three cancer cell 
      lines mainly depended on glycolysis (70-80%). Anti-mitochondrial drugs 
      (oligomycin, casiopeina II-gly, and methoxy-TEA) and celecoxib, at doses used to 
      block OxPhos, significantly decreased TN cancer cell proliferation (IC(50) = 2-20 
      muM), migration capacity (10-90%), and invasiveness (25-65%). The present data 
      support the use of mitochondrially targeted inhibitors for the treatment of TN 
      breast carcinoma.
FAU - Pacheco-Velazquez, Silvia Cecilia
AU  - Pacheco-Velazquez SC
AD  - Departamento de Bioquimica , Instituto Nacional de Cardiologia , 14080 Tlalpan , 
      CDMX , Mexico.
FAU - Robledo-Cadena, Diana Xochiquetzal
AU  - Robledo-Cadena DX
AD  - Departamento de Bioquimica , Instituto Nacional de Cardiologia , 14080 Tlalpan , 
      CDMX , Mexico.
FAU - Hernandez-Resendiz, Ileana
AU  - Hernandez-Resendiz I
AD  - Departamento de Bioquimica , Instituto Nacional de Cardiologia , 14080 Tlalpan , 
      CDMX , Mexico.
FAU - Gallardo-Perez, Juan Carlos
AU  - Gallardo-Perez JC
AD  - Departamento de Bioquimica , Instituto Nacional de Cardiologia , 14080 Tlalpan , 
      CDMX , Mexico.
FAU - Moreno-Sanchez, Rafael
AU  - Moreno-Sanchez R
AD  - Departamento de Bioquimica , Instituto Nacional de Cardiologia , 14080 Tlalpan , 
      CDMX , Mexico.
FAU - Rodriguez-Enriquez, Sara
AU  - Rodriguez-Enriquez S
AUID- ORCID: 0000-0002-0822-1233
AD  - Departamento de Bioquimica , Instituto Nacional de Cardiologia , 14080 Tlalpan , 
      CDMX , Mexico.
AD  - Laboratorio de Medicina Traslacional , Instituto Nacional de Cancerologia , 14080 
      Tlalpan , CDMX , Mexico.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180523
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Drug Screening Assays, Antitumor
MH  - Energy Metabolism/*drug effects
MH  - Female
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Mice
MH  - Mitochondria/*drug effects/metabolism
MH  - Oxidative Phosphorylation/drug effects
MH  - Triple Negative Breast Neoplasms/*drug therapy/pathology
OTO - NOTNLM
OT  - breast cancer
OT  - celecoxib
OT  - energy metabolism drugs
OT  - glycolysis
OT  - metastasis
OT  - oxidative phosphorylation
EDAT- 2018/05/11 06:00
MHDA- 2019/07/04 06:00
CRDT- 2018/05/11 06:00
PHST- 2018/05/11 06:00 [pubmed]
PHST- 2019/07/04 06:00 [medline]
PHST- 2018/05/11 06:00 [entrez]
AID - 10.1021/acs.molpharmaceut.8b00015 [doi]
PST - ppublish
SO  - Mol Pharm. 2018 Jun 4;15(6):2151-2164. doi: 10.1021/acs.molpharmaceut.8b00015. 
      Epub 2018 May 23.