Dietary leucine supplementation minimises tumour-induced damage in placental tissues of pregnant, tumour-bearing rats

Author(s)

Gomes Cruz, Bread Leandro ^[1] ; da Silva, Priscila Cristina ^[1] ; Tomasin, Rebeka ^[1] ; Oliveira, Andre Gustavo ^[1] ; Viana, Lais Rosa ^[1] ; Salomao, Emilianne Miguel ^[1] ; Cintra Gomes-Marcondes, Maria Cristina ^{[1, 2]}

Affiliation

^[1] Univ Estadual Campinas, State Univ Campinas, Inst Biol, Dept Struct & Funct Biol, CP 6109, BR-13083862 Campinas, SP - Brazil

^[2] Rua Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil

• Document type: Journal article
• Source: BMC CANCER; v. 16, FEB 4 2016.
• Web of Science Citations: 4

Abstract

Background: The occurrence of cancer during pregnancy merges two complex, poorly understood metabolic and hormonal conditions. This association can exacerbate the conditions of both the mother and the foetus. The branched-chain amino acid leucine enhances cellular activity, particularly by increasing protein synthesis. This study aimed to analyse the modulatory effect of a leucine-rich diet on direct and indirect tumour-induced placental damage. This was accomplished by evaluating the expression of genes involved in protein synthesis and degradation and assessing anti-oxidant enzyme activity in placental tissues collected from pregnant, tumour-bearing rats. Results: Pregnant rats were either implanted with Walker 256 tumour cells or injected with ascitic fluid (to study the indirect effects of tumour growth) and then fed a leucine-rich diet. Animals in a control group underwent the same procedures but were fed a normal diet. On the 20th day of pregnancy, tumour growth was observed. Dams fed a normoprotein diet showed the greatest tumour growth. Injection with ascitic fluid mimicked the effects of tumour growth. Decreased placental protein synthesis and increased protein degradation were observed in both the tumour-bearing and the ascitic fluid-injected groups that were fed a normoprotein diet. These effects resulted in low placental DNA and protein content and high lipid peroxidation (measured by malondialdehyde content). Decreased placental protein synthesis-related gene expression was observed in the tumour group concomitant with increased expression of genes encoding protein degradation-associated proteins and proteolytic subunits. Conclusions: Consumption of a leucine-rich diet counteracted the effects produced by tumour growth and injection with ascitic fluid. The diet enhanced cell signalling, ameliorated deficiencies in DNA and protein content, and balanced protein synthesis and degradation processes in the placenta. The improvements in cell signalling included changes in the mTOR/eIF pathway. In conclusion, consumption of a leucine-rich diet improved placental metabolism and cell signalling in tumour-bearing rats, and these changes reduced the deleterious effects caused by tumour growth. (AU)

• FAPESP's process: 11/08276-0 - Modultation of L-leucine on cell signaling and metabolic pathways of muscle protein metabolism in Walker 256 tumor-bearing rats.
• Grantee: Bread Leandro Gomes da Cruz
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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 Opportunities: Regular Research Grants
• FAPESP's process: 10/00209-9 - Nutritional supplementation and cancer cachexia. Biochemical and molecular studies
• Grantee: Maria Cristina Cintra Gomes Marcondes
• Support Opportunities: Regular Research Grants