Laboratory of Metabolism Control, Ribeirão Preto Medical School, Department of Physiology, University of São Paulo, Ribeirão Preto, State of São Paulo, Brazil.
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.
BMC Complement Med Ther. 2021 Jan 7;21(1):20. doi: 10.1186/s12906-020-03190-1.
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.
Ehrlich tumor was used as model of cancer cachexia. Ascitic Ehrlich tumor cells were collected, processed and inoculated subcutaneously in saline solution (1 × 10/100 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.
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.
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.
癌症是一种由细胞失控增殖引起的多因素疾病。约 50-80%的癌症患者会出现恶病质，这是一种与死亡率和发病率增加相关的复杂代谢综合征。然而，临床上尚无有效的恶病质治疗方法。Vochysia tucanorum Mart. 是巴西“塞拉多”的三种常见植物之一。V. tucanorum 的丁醇部分（Fr-BuVt）富含具有各种生物活性的三萜类化合物，可能是测试癌症恶病质综合征的有趣选择。因此，本研究旨在探讨 Fr-BuVt 的抗肿瘤活性及其对恶病质发展的潜在作用。
艾氏腹水瘤被用作癌症恶病质的模型。收集、处理并皮下接种艾氏腹水癌细胞于生理盐水溶液中（1×10/100μl；活力≥95%），以获得实体艾氏腹水癌。接种后，用 Fr-BuVt（200mg/kg）连续 14 天通过灌胃对实体艾氏腹水癌荷瘤小鼠进行治疗。在治疗期间测量体重和肿瘤体积。切除肿瘤，称重并适当处理，通过 Western Blot 测量参与凋亡和增殖过程的关键蛋白的含量和磷酸化水平。切除肌肉和脂肪组织称重。收集血清以测量细胞因子水平和能量血液标志物。
Fr-BuVt（200mg/kg，14 天）治疗可降低实体艾氏腹水瘤的体积和重量，同时增加促凋亡蛋白 caspase-3 和 BAX 的表达，还降低了参与增殖的蛋白 NFκB、mTOR 和 ERK 的表达。此外，我们的数据表明，Fr-BuVt 的给药能够防止艾氏腹水癌荷瘤小鼠恶病质的发生，因为它防止了体重下降以及肌肉和脂肪组织的丢失。此外，还观察到一些血液参数的改善，例如细胞因子 TNF-α 和 IL-6 水平的降低。
该研究表明 Fr-BuVt 具有抗肿瘤活性，并可防止艾氏腹水瘤模型中恶病质的发生。因此，Fr-BuVt 可能是治疗癌症恶病质的一种替代方法。
