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

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.

Antitumor Activity of Ligustilide Against Ehrlich Solid Carcinoma in Rats via Inhibition of Proliferation and Activation of Autophagy

“…It is a key factor in autophagy induction and plays a vital role in cell growth, proliferation, autophagy, and survival. Promising results have been seen from testing mTOR inhibitors against tumor cells [20]. We found that ligustilide significantly reduced the ESC-induced elevation in the expression of mTOR.…”

“…mTOR functions as a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription [20]. In ESC, mTOR had elevated gene expression and protein levels compared to the control group.…”

Evaluation of the antitumor and antioxidant effects of jatobá (Hymenaea courbaril) extracts / Avaliação do efeito antitumoral e antioxidante de extratos do jatobá (Hymenaea courbaril)

“…According to Machado and Melo Júnior 25 , weight parameters, such as the weight of tumors and variations in body mass, are extremely valuable to monitor the effects of antineoplastic drugs. Cancer cachexia is a multifactorial syndrome that affects the prognosis of the disease in 50% of patients 26 , leading to a progressively negative energy balance that impairs the functioning of the body and affects various organs, such as the liver and brain 27 . Muscle, lipids, and carbohydrates are used by the body, and by the tumor itself, as substrates for hypercatabolism, causing weight loss, the main characteristic of the syndrome 27 .…”

“…Cancer cachexia is a multifactorial syndrome that affects the prognosis of the disease in 50% of patients 26 , leading to a progressively negative energy balance that impairs the functioning of the body and affects various organs, such as the liver and brain 27 . Muscle, lipids, and carbohydrates are used by the body, and by the tumor itself, as substrates for hypercatabolism, causing weight loss, the main characteristic of the syndrome 27 . Solid Ehrlich tumor is an efficient model for the study of the effects of cachexia, reproducing the systemic proinflammatory effects that generate skeletal muscle loss and lipolysis 26 .…”

Features and applications of Ehrlich tumor model in cancer studies: a literature review

“…In addition to this versatility, the advantages of the model include fast tumor growth and high rates of tumor occurrence after transplantation ( 60 ). The antineoplastic potential of a wide variety of substances has already been tested, including probiotics, polysaccharides, oligosaccharides, spices, plant extracts, isolated compounds, seaweed, off-label drugs alone or in combination with routine anticancer drugs, and countless variations of formulations, including nanoparticles ( 8 , 16 - 19 , 61 - 65 ). Table 2 shows some applications of solid and liquid models of Ehrlich carcinoma in preclinical studies.…”