Vochysia tucanorum Mart. butanol fraction presents antitumoral activity in vivo and prevents the installation of cachexia in solid Ehrlich tumor model

Henrique Jorge Novaes Morgan,Aislan Quintiliano Delgado,Anne Lígia Dokkedal,José Roberto Bosqueiro,Nathalia Aparecida De Paula Camaforte,Luiz Leonardo Saldanha

doi:10.1186/s12906-020-03190-1

Henrique Jorge Novaes Morgan, Aislan Quintiliano Delgado + Show 4 more

Open Access

https://doi.org/10.1186/s12906-020-03190-1

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Abstract

BackgroundCancer 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.MethodsEhrlich 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.ResultsThe 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.ConclusionsThe 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.

Highlights

Cancer is a multifactorial disease caused by uncontrolled proliferation of cells
We evaluated the administration of butanolic fraction of V. tucanorum Mart. in Ehrlich tumor model of cachexia in mice through molecular, biochemical and clinical parameters analysis
Identification of constituents from n-butanol fraction The constituents from the Butanolic fraction of Vochysia tucanorum Mart (Fr-BuVt) were identified based on experimental retention time and Mass spectrometry (MS)/MS data (Fig. 2, Table 1) obtained in comparison with available data in literature [9, 28]

Summary

Introduction

About 50–80% of cancer patients develop cachexia, a complex metabolic syndrome associated with an increase of mortality and morbidity. There are no effective therapies in medical clinic for cancer cachexia. 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. It increases the morbidity and mortality of the patients, besides reduces tolerance to anticancer therapies [2]. Cachexia is a complex metabolic syndrome, which is associated with chronic and immunosuppressive diseases like AIDS, cirrhosis, renal and cardiac insufficiency. The greatest representativeness is found in cancer patients, since about 80% of them develop this syndrome [3, 4]. The substrates from the hypercatabolism of muscle, lipids and carbohydrate are used by both host and tumor, and are the most responsible for the weight loss, the main characteristic of this syndrome [5]

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