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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Metformin treatment modulates the tumour-induced wasting effects in muscle protein metabolism minimising the cachexia in tumour-bearing rats

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Author(s):
Oliveira, Andre G. [1] ; Gomes-Marcondes, Maria Cristina C. [1]
Total Authors: 2
Affiliation:
[1] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Struct & Funct Biol, Rua Monteiro Lobato 255, CP 6109, BR-13083862 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: BMC CANCER; v. 16, JUL 7 2016.
Web of Science Citations: 17
Abstract

Background: Cancer-cachexia state frequently induces both fat and protein wasting, leading to death. In this way, the knowledge of the mechanism of drugs and their side effects can be a new feature to treat and to have success, contributing to a better life quality for these patients. Metformin is an oral drug used in type 2 diabetes mellitus, showing inhibitory effect on proliferation in some neoplastic cells. For this reason, we evaluated its modulatory effect on Walker-256 tumour evolution and also on protein metabolism in gastrocnemius muscle and body composition. Methods: Wistar rats received or not tumour implant and metformin treatment and were distributed into four groups, as followed: control (C), Walker 256 tumour-bearing (W), metformin-treated (M) and tumour-bearing treated with metformin (WM). Animals were weighed three times a week, and after cachexia state has been detected, the rats were euthanised and muscle and tumour excised and analysed by biochemical and molecular assays. Results: Tumour growth promoted some deleterious effects on chemical body composition, increasing water and decreasing fat percentage, and reducing lean body mass. In muscle tissue, tumour led to a decreased protein synthesis and an increased proteolysis, showing the higher activity of the ubiquitin-proteasome pathway. On the other hand, the metformin treatment likely minimised the tumour-induced wasting state; in this way, this treatment ameliorated chemical body composition, reduced the higher activities of proteolytic enzymes and decreased the protein waste. Conclusion: Metformin treatment not only decreases the tumour growth but also improves the protein metabolism in gastrocnemius muscle in tumour-bearing rats. (AU)

FAPESP's process: 13/16115-1 - Biochemical and molecular mechanisms of cachexia. effects of Walker factor and leucine supplementation on myotube cell culture
Grantee:Maria Cristina Cintra Gomes Marcondes
Support type: Regular Research Grants
FAPESP's process: 08/07737-0 - Effects of metformin treatment associated to leucine rich-diet on protein metabolism in tumour-bearing rats
Grantee:André Gustavo de Oliveira
Support type: Scholarships in Brazil - Master
FAPESP's process: 10/00209-9 - Nutritional supplementation and cancer cachexia. Biochemical and molecular studies
Grantee:Maria Cristina Cintra Gomes Marcondes
Support type: Regular Research Grants
FAPESP's process: 14/13334-7 - Nutrition and cancer: metabolomic, and proteomic profile of muscle, placental, fetal, and tumor cell signaling pathways in Walker-256 tumour-bearing pregnant rats submitted to leucine nutritional supplementation
Grantee:Maria Cristina Cintra Gomes Marcondes
Support type: Regular Research Grants