Myrtenal-induced V-ATPase inhibition - A toxicity mechanism behind tumor cell death and suppressed migration and invasion in melanoma.
Animals
Antineoplastic Agents
/ pharmacology
Bicyclic Monoterpenes
Cell Death
Cell Line, Tumor
Cell Membrane
/ metabolism
Cell Movement
Disease Models, Animal
Drug Resistance, Neoplasm
Electrodes
Humans
Hydrogen-Ion Concentration
Male
Melanoma
/ drug therapy
Melanoma, Experimental
Mice
Mice, Inbred C57BL
Neoplasm Invasiveness
Neoplasm Metastasis
/ drug therapy
Protons
Skin Neoplasms
/ drug therapy
Terpenes
/ pharmacology
Vacuolar Proton-Translocating ATPases
/ antagonists & inhibitors
Anti-melanoma drugs
Bioactive terpenes
Proton pumps inhibitors
Tumor acidification
pH signatures
Journal
Biochimica et biophysica acta. General subjects
ISSN: 1872-8006
Titre abrégé: Biochim Biophys Acta Gen Subj
Pays: Netherlands
ID NLM: 101731726
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
11
02
2018
revised:
09
09
2018
accepted:
10
09
2018
pubmed:
4
10
2018
medline:
17
8
2019
entrez:
4
10
2018
Statut:
ppublish
Résumé
Metastatic tumor cells have acidic extracellular pH and differential electrochemical H The Myrtenal anticancer toxicity was evaluated in vitro using murine (B16F0 and B16F10) and human (SkMel-5) melanoma cell lines, and in in vivo mouse metastatic dissemination model. Proton flux and extracellular acidification were directly evaluated at the surface of living cells using a non-invasive selective ion electrode approach. The inhibition of V-ATPases by 100 μM Myrtenal disrupted the electrochemical H These data revealed the therapeutic potential of Myrtenal as inhibitor of melanoma progression proposing a mechanism of action by which once inhibited by this monoterpene the proton pumps fail to activate cancer-related differential electrochemical gradients and H The work represents a new mechanistic strategy for contention of melanoma, the most aggressive and deadly form of cutaneous neoplasm, and highlights Myrtenal, other related monoterpenes and derivatives as promising proton pump inhibitors with high chemotherapeutic potential.
Sections du résumé
BACKGROUND
Metastatic tumor cells have acidic extracellular pH and differential electrochemical H
METHODS
The Myrtenal anticancer toxicity was evaluated in vitro using murine (B16F0 and B16F10) and human (SkMel-5) melanoma cell lines, and in in vivo mouse metastatic dissemination model. Proton flux and extracellular acidification were directly evaluated at the surface of living cells using a non-invasive selective ion electrode approach.
RESULTS
The inhibition of V-ATPases by 100 μM Myrtenal disrupted the electrochemical H
CONCLUSIONS
These data revealed the therapeutic potential of Myrtenal as inhibitor of melanoma progression proposing a mechanism of action by which once inhibited by this monoterpene the proton pumps fail to activate cancer-related differential electrochemical gradients and H
GENERAL SIGNIFICANCE
The work represents a new mechanistic strategy for contention of melanoma, the most aggressive and deadly form of cutaneous neoplasm, and highlights Myrtenal, other related monoterpenes and derivatives as promising proton pump inhibitors with high chemotherapeutic potential.
Identifiants
pubmed: 30279148
pii: S0304-4165(18)30294-0
doi: 10.1016/j.bbagen.2018.09.006
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Bicyclic Monoterpenes
0
Protons
0
Terpenes
0
myrtenal
8J97443QRZ
Vacuolar Proton-Translocating ATPases
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
1-12Informations de copyright
Copyright © 2018 Elsevier B.V. All rights reserved.