Henrique Jorge Novaes Morgan1, Aislan Quintiliano Delgado2, Luiz Leonardo Saldanha3, Nathalia Aparecida De Paula Camaforte2, Anne Lígia Dokkedal3, José Roberto Bosqueiro4. 1. Laboratory of Metabolism Control, Ribeirão Preto Medical School, Department of Physiology, University of São Paulo, Ribeirão Preto, State of São Paulo, Brazil. 2. Laboratory of Endocrine Pancreas Physiology, Faculty of Science, Department of Physical Education, São Paulo State University, Av. Eng. Luiz Edmundo Carrijo Coube 14-01, Bauru, São Paulo, Postal Code: 17033-360, Brazil. 3. Laboratory of Natural Products Chemistry, Faculty of Science, Department of Biological Sciences, São Paulo State University, Bauru, State of São Paulo, Brazil. 4. Laboratory of Endocrine Pancreas Physiology, Faculty of Science, Department of Physical Education, São Paulo State University, Av. Eng. Luiz Edmundo Carrijo Coube 14-01, Bauru, São Paulo, Postal Code: 17033-360, Brazil. jose.bosqueiro@unesp.br.
Abstract
BACKGROUND: Cancer is a multifactorial disease caused by uncontrolled proliferation of cells. About 50-80% of cancer patients develop cachexia, a complex metabolic syndrome associated with an increase of mortality and morbidity. However, there are no effective therapies in medical clinic for cancer cachexia. Vochysia tucanorum Mart. is a common three of the Brazilian "Cerrado". The butanolic fraction of V. tucanorum (Fr-BuVt), very rich in triterpenes with various biological activities, might be interesting in being tested in cancer cachexia syndrome. Hence, the present study was undertaken to investigate the antitumoral activity of Fr-BuVt and its potential against cachexia development. METHODS: Ehrlich tumor was used as model of cancer cachexia. Ascitic Ehrlich tumor cells were collected, processed and inoculated subcutaneously in saline solution (1 × 107/100 μl; ≥95% viability) for the obtention of solid Ehrlich carcinoma. After inoculation, solid Ehrlich carcinoma-bearing mice were treated by 14 consecutive days by gavage with Fr-BuVt (200 mg/kg). Body weight and tumor volume were measure during the treatment period. Tumors were removed, weighed and properly processed to measure the content and phosphorylation levels of key-proteins involved to apoptotic and proliferation process by Western Blot. Muscles and adipose tissues were removed for weighed. Serum was collected to cytokines levels and energetic blood markers measurements. RESULTS: The treatment with the Fr-BuVt (200 mg/kg, 14 days) decreased the solid Ehrlich tumor volume and weight besides increased the expression of the pro-apoptotic proteins caspase-3 and BAX, but also decreased the expression of the proteins involved in proliferation NFκB, mTOR and ERK. In addition, our data shows that the administration of Fr-BuVt was able to prevent the installation of cancer cachexia in Ehrlich carcinoma-bearing mice, since prevented the loss of body weight, as well as the loss of muscle and adipose tissue. Moreover, an improvement in some blood parameters such as decrease in cytokines TNF-α and IL-6 levels is observed. CONCLUSIONS: The study revealed that Fr-BuVt has antitumoral activity and prevent installation of cancer cachexia in Ehrlich model. Therefore, Fr-BuVt may represent an alternative treatment for cancer cachexia.
BACKGROUND:Cancer is a multifactorial disease caused by uncontrolled proliferation of cells. About 50-80% of cancerpatients develop cachexia, a complex metabolic syndrome associated with an increase of mortality and morbidity. However, there are no effective therapies in medical clinic for cancer cachexia. Vochysia tucanorum Mart. is a common three of the Brazilian "Cerrado". The butanolic fraction of V. tucanorum (Fr-BuVt), very rich in triterpenes with various biological activities, might be interesting in being tested in cancer cachexia syndrome. Hence, the present study was undertaken to investigate the antitumoral activity of Fr-BuVt and its potential against cachexia development. METHODS:Ehrlich tumor was used as model of cancer cachexia. Ascitic Ehrlich tumor cells were collected, processed and inoculated subcutaneously in saline solution (1 × 107/100 μl; ≥95% viability) for the obtention of solid Ehrlich carcinoma. After inoculation, solid Ehrlich carcinoma-bearing mice were treated by 14 consecutive days by gavage with Fr-BuVt (200 mg/kg). Body weight and tumor volume were measure during the treatment period. Tumors were removed, weighed and properly processed to measure the content and phosphorylation levels of key-proteins involved to apoptotic and proliferation process by Western Blot. Muscles and adipose tissues were removed for weighed. Serum was collected to cytokines levels and energetic blood markers measurements. RESULTS: The treatment with the Fr-BuVt (200 mg/kg, 14 days) decreased the solid Ehrlich tumor volume and weight besides increased the expression of the pro-apoptotic proteins caspase-3 and BAX, but also decreased the expression of the proteins involved in proliferation NFκB, mTOR and ERK. In addition, our data shows that the administration of Fr-BuVt was able to prevent the installation of cancer cachexia in Ehrlich carcinoma-bearing mice, since prevented the loss of body weight, as well as the loss of muscle and adipose tissue. Moreover, an improvement in some blood parameters such as decrease in cytokines TNF-α and IL-6 levels is observed. CONCLUSIONS: The study revealed that Fr-BuVt has antitumoral activity and prevent installation of cancer cachexia in Ehrlich model. Therefore, Fr-BuVt may represent an alternative treatment for cancer cachexia.
Entities:
Keywords:
Anti-apoptotic; Anti-proliferation; Cancer cachexia; Metabolic syndrome; Triterpenes
Authors: Carlos K Katashima; Vagner R Silva; Tatyanne L Gomes; Claude Pichard; Gustavo D Pimentel Journal: Obes Rev Date: 2017-03-23 Impact factor: 9.213
Authors: Nathalia Ap De Paula Camaforte; Luiz Leonardo Saldanha; Priscilla Maria Ponce Vareda; João M Rezende-Neto; Mario R Senger; Aislan Q Delgado; Henrique J N Morgan; Natalia Moretti Violato; Laís Goyos Pieroni; Anne Lígia Dokkedal; Floriano P Silva-Júnior; José Roberto Bosqueiro Journal: Pharm Biol Date: 2019-12 Impact factor: 3.503