Journal article

Mitochondrial Targeting of Metformin Enhances Its Activity against Pancreatic Cancer

Stepana Boukalova, Jan Stursa, Lukas Werner, Zuzana Ezrova, Jiri Cerny, Ayenachew Bezawork-Geleta, Alena Pecinova, Lanfeng Dong, Zdenek Drahota, Jiri Neuzil

MOLECULAR CANCER THERAPEUTICS | AMER ASSOC CANCER RESEARCH | Published : 2016

Abstract

Pancreatic cancer is one 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 mo..

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Grants

Awarded by Czech Science Foundation


Awarded by Czech Ministry of Health grant


Awarded by BIOCEV from ERDF


Awarded by Mitenal from ERDF


Awarded by Ministry of Education, Youth and Sports of the Czech Republic at CZ-OPEN-SCREEN: National infrastructure for chemical biology


Funding Acknowledgements

This work was supported in part by Australian Research Council Discovery grant, Czech Science Foundation grant (GA15-02203S), and Czech Ministry of Health grant (AZV 16-31604.A) to J. Neuzil. Further support was provided by BIOCEV CZ.1.05/1.1.00/02.0109 and Mitenal CZ.2.16/3.1.00/21531 from the ERDF, RVO: 86652036 and the Ministry of Education, Youth and Sports of the Czech Republic (LO1220) at the CZ-OPEN-SCREEN: National infrastructure for chemical biology.