Mitochondrial Targeting of Metformin Enhances Its Activity against Pancreatic Cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F16%3A43902059" target="_blank" >RIV/60461373:22330/16:43902059 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/86652036:_____/16:00469007 RIV/67985823:_____/16:00469007 RIV/00179906:_____/16:10331057

Výsledek na webu

<a href="http://dx.doi.org/10.1158/1535-7163.MCT-15-1021" target="_blank" >http://dx.doi.org/10.1158/1535-7163.MCT-15-1021</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1158/1535-7163.MCT-15-1021" target="_blank" >10.1158/1535-7163.MCT-15-1021</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mitochondrial Targeting of Metformin Enhances Its Activity against Pancreatic Cancer

Popis výsledku v původním jazyce

Pancreatic cancer isone of the hardest-to-treat types of neoplastic diseases. Metformin, a widely prescribed drug against type 2 diabetes mellitus, is being trialed as an agent against pancreatic cancer, although its efficacy is low. With the idea of delivering metformin to its molecular target, the mitochondrial complex I (CI), we tagged the agent with the mitochondrial vector, triphenylphosphonium group. Mitochondrially targeted metformin (MitoMet) was found to kill a panel of pancreatic cancer cells three to four orders of magnitude more efficiently than found for the parental compound. Respiration assessment documented CI as the molecular target for MitoMet, which was corroborated by molecular modeling. MitoMet also efficiently suppressed pancreatic tumors in three mouse models. We propose that the novel mitochondrially targeted agent is clinically highly intriguing, and it has a potential to greatly improve the bleak prospects of patients with pancreatic cancer.

Název v anglickém jazyce

Mitochondrial Targeting of Metformin Enhances Its Activity against Pancreatic Cancer

Popis výsledku anglicky

Pancreatic cancer isone of the hardest-to-treat types of neoplastic diseases. Metformin, a widely prescribed drug against type 2 diabetes mellitus, is being trialed as an agent against pancreatic cancer, although its efficacy is low. With the idea of delivering metformin to its molecular target, the mitochondrial complex I (CI), we tagged the agent with the mitochondrial vector, triphenylphosphonium group. Mitochondrially targeted metformin (MitoMet) was found to kill a panel of pancreatic cancer cells three to four orders of magnitude more efficiently than found for the parental compound. Respiration assessment documented CI as the molecular target for MitoMet, which was corroborated by molecular modeling. MitoMet also efficiently suppressed pancreatic tumors in three mouse models. We propose that the novel mitochondrially targeted agent is clinically highly intriguing, and it has a potential to greatly improve the bleak prospects of patients with pancreatic cancer.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular Cancer Therapeutics

ISSN

1535-7163

e-ISSN

—

Svazek periodika

15

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

2875-2886

Kód UT WoS článku

000390092800006

EID výsledku v databázi Scopus

2-s2.0-85008312167