Beta-elemene inhibits breast cancer metastasis through blocking pyruvate kinase M2 dimerization and nuclear translocation.
Aerobiosis
Animals
Breast Neoplasms
/ enzymology
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Nucleus
/ drug effects
Cysteine
/ pharmacology
ErbB Receptors
/ metabolism
Female
Fructosediphosphates
/ pharmacology
Gene Expression Regulation, Neoplastic
/ drug effects
Glucose Transporter Type 1
/ metabolism
Glycolysis
/ drug effects
Humans
Mice, Inbred BALB C
Mice, Nude
Models, Biological
Neoplasm Invasiveness
Neoplasm Metastasis
Protein Multimerization
/ drug effects
Protein Transport
/ drug effects
Pyruvate Kinase
/ metabolism
Sesquiterpenes
/ pharmacology
Signal Transduction
/ drug effects
aerobic glycolysis
beta-elemene
breast cancer
metastasis
pyruvate kinase M2
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
27
02
2019
revised:
08
06
2019
accepted:
05
07
2019
pubmed:
26
7
2019
medline:
4
9
2020
entrez:
26
7
2019
Statut:
ppublish
Résumé
Pyruvate kinase M2 (PKM2), playing a central role in regulating aerobic glycolysis, was considered as a promising target for cancer therapy. However, its role in cancer metastasis is rarely known. Here, we found a tight relationship between PKM2 and breast cancer metastasis, demonstrated by the findings that beta-elemene (β-elemene), an approved drug for complementary cancer therapy, exerted distinct anti-metastatic activity dependent on PKM2. The results indicated that β-elemene inhibited breast cancer cell migration, invasion in vitro as well as metastases in vivo. β-Elemene further inhibited the process of aerobic glycolysis and decreased the utilization of glucose and the production of pyruvate and lactate through suppressing pyruvate kinase activity by modulating the transformation of dimeric and tetrameric forms of PKM2. Further analysis revealed that β-elemene suppressed aerobic glycolysis by blocking PKM2 nuclear translocation and the expression of EGFR, GLUT1 and LDHA by influencing the expression of importin α5. Furthermore, the effect of β-elemene on migration, invasion, PKM2 transformation, and nuclear translocation could be reversed in part by fructose-1,6-bisphosphate (FBP) and L-cysteine. Taken together, tetrameric transformation and nuclear translocation of PKM2 are essential for cancer metastasis, and β-elemene inhibited breast cancer metastasis via blocking aerobic glycolysis mediated by dimeric PKM2 transformation and nuclear translocation, being a promising anti-metastatic agent from natural compounds.
Identifiants
pubmed: 31343107
doi: 10.1111/jcmm.14568
pmc: PMC6787513
doi:
Substances chimiques
Fructosediphosphates
0
Glucose Transporter Type 1
0
Sesquiterpenes
0
beta-elemene
0
Pyruvate Kinase
EC 2.7.1.40
ErbB Receptors
EC 2.7.10.1
Cysteine
K848JZ4886
fructose-1,6-diphosphate
M7522JYX1H
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6846-6858Informations de copyright
© 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicineand John Wiley & Sons Ltd.
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