Metformin’s Anti-Cancer Properties Clarified In An Obesity Cell Model Of Pancreatic Cancer
Posted Aug 20 2013 3:00pm
SiDMAP and University of Arizona researchers gain a clearer understanding of the mechanistic properties of the drug metformin. The study may explain the mechanism of how elevated circulating cholesterol, which is an important disease modifying factor in the diabetic pancreatic cancer patient, alters cellular metabolism in a way that metformin’s known fatty acid synthase inhibiting effect becomes a cell growth limiting factor.
SiDMAP, LLC, a leading provider of targeted 13C tracer fate association studies and biomarker development services, announces the publication of findings that metformin inhibits carbon flux towards new fatty acid synthesis in the presence of cholesterol, a known diseases factor in obesity and diabetes, to facilitate pancreatic cancer growth. The integrated nutritional and 13C Isotopolome-Wide Association Study with cholesterol administration to pancreatic cancer cell lines, is published in the official journal of the Metabolomics Society in collaboration with scientists at the University of Arizona, Department of Nutritional Sciences and the University of Arizona Cancer Center.
SiDMAP scientists provided the metabolic analysis for the study using pancreatic cancer cells expressing K-ras differently, which is a common mutation in pancreatic cancer. They integrated positional 13C labeling in multiple metabolic products in diverse sampling sites from a single 13C labeled glucose tracer. It is known that stable expression of K-ras induces a pancreatic cancer metabolic phenotype that competes for new acetate, formed from glucose, in the cholesterol and fatty acid producing pathways. “Cholesterol administration diverts new acetate towards fatty acid synthesis, which provides the contextual factor for metformin to inhibit new fatty acid synthesis, cell membrane turnover and potentially cell growth,” said Dr. Laszlo G. Boros, Chief Scientist at SiDMAP.
“The study may explain the mechanism of how elevated circulating cholesterol, which is an important disease modifying factor in the diabetic pancreatic cancer patient, alters cellular metabolism in a way that metformin’s known fatty acid synthase inhibiting effect becomes a cell growth limiting factor,” said Dr. Emmanuelle J. Meuillet, the study’s lead investigator.
The work is published as a Springer Open Access article, online first, in the journal Metabolomics and is titled, “Contextual inhibition of fatty acid synthesis by metformin involves glucose-derived acetyl-CoA and cholesterol in pancreatic tumor cells.” http://link.springer.com/article/10.1007%2Fs11306-013-0555-4
The study was supported by the Hirshberg Foundation for Pancreatic Cancer Research (http://www.pancreatic.org). “It is a key goal of the Foundation to bring lead scientists together to shed light on well-known, yet unexplained disease controlling mechanism of national research interest in obesity, diabetes and pancreatic cancer. This research is significant because it is in line with the National Cancer Institute’s quest to find bold new approaches to answer the perplexing scientific question of why the mechanism of a drug like metformin, which is generally used for other indications, protects against cancer incidence and mortality,“ said Agi Hirshberg, President of the Foundation.
SiDMAP provides flux-based, metabolic profiling services to pharmaceutical, biotech and research organizations seeking to enhance their drug development processes, and develop further insights into a drug’s mechanism of action and disease states. SiDMAP’s unique tracer technology measures metabolic pathway flux to gain unique insights into cell function. A SiDMAP assay provides clients with an accurate, dynamic metabolic analysis of a compound’s biological impact in both in vitro and in vivo systems, before a company spends millions more on development and clinical trials. SiDMAP is headquartered in Los Angeles, California.