Mitochondrial targeting of metformin enhances its activity against pancreatic cancer

Boukalova, Stepana, Stursa, Jan, Werner, Lukas, Ezrova, Zuzana, Cerny, Jiri, Bezawork-Geleta, Ayenachew, Pecinova, Alena, Dong, Lanfeng, Drahota, Zdenek and Neuzil, Jiri (2016) Mitochondrial targeting of metformin enhances its activity against pancreatic cancer. Molecular Cancer Therapeutics, 15 12: 2875-2886. doi:10.1158/1535-7163.MCT-15-1021


Author Boukalova, Stepana
Stursa, Jan
Werner, Lukas
Ezrova, Zuzana
Cerny, Jiri
Bezawork-Geleta, Ayenachew
Pecinova, Alena
Dong, Lanfeng
Drahota, Zdenek
Neuzil, Jiri
Title Mitochondrial targeting of metformin enhances its activity against pancreatic cancer
Journal name Molecular Cancer Therapeutics   Check publisher's open access policy
ISSN 1538-8514
1535-7163
Publication date 2016-12-01
Year available 2016
Sub-type Article (original research)
DOI 10.1158/1535-7163.MCT-15-1021
Open Access Status Not yet assessed
Volume 15
Issue 12
Start page 2875
End page 2886
Total pages 12
Place of publication Philadelphia, PA United States
Publisher American Association for Cancer Research
Language eng
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 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 12 Jun 2017, 09:53:01 EST by Kirstie Asmussen on behalf of Queensland Brain Institute