Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará (UECE), Avenida Dr Silas Munguba, 1700, Campus do Itaperi, CEP 60.740-002 Fortaleza, CE, Brazil.
Laboratório de Biologia e Genética Molecular, Departamento de Patologia e Medicina Legal, Universidade Federal do Ceará, Rua Alexandre Baraúna, 994, Rodolfo Teófilo, CEP 60.430-160 Fortaleza, CE, Brazil.
J Ethnopharmacol. 2018 Jun 28;220:159-168. doi: 10.1016/j.jep.2017.09.043. Epub 2017 Oct 24.
In Brazil, latex of Himatanthus drasticus is used to treat inflammation, wound healing and cancer. The present study evaluated the antitumoral potential of H. drasticus latex (HdCL) in Sarcoma 180-bearing mice (S180).
HdCL was obtained in Crato-CE, Brazil. Qualitative phytochemicals assays, nuclear magnetic resonance (NMR) and microbiological analyzes were performed. Swiss mice were divided into six groups, according to tumor forms: 1) ascitic model, GI (Control; 0.9% saline), GII (Sasc) and GIII (Sasc/HdCL/14 days); 2) solid model, GIV (Control; 0.9% saline), GV (Ssol) and GVI (Ssol/HdCL/10 days). HdCL and 0.9% saline were administered at 0.2 mL, SID, by gavage, for 10 or 14 days. For ascitic model, 0.5 mL of S180 suspension (4×10 cells/mL) was inoculated intraperitoneally and for solid model, cells were inoculated subcutaneously (25 µL) on the right hind paw of mice. Blood samples were collected for hematological and oxidative stress evaluation. Thickness, volume and weight of paws were measured in solid model. After euthanasia, spleen, liver and kidney were collected in order to assess the relative organ weight. Tissue fragments of paws and popliteal lymph nodes (PLN) were analyzed by H&E and CD4, CD8, HSP-60 and Foxp3 immunohistochemistry.
HdCL presented milky aspect and pinkish supernatant. Phenols, flavonols, flavanones, free steroids and cinnamoyl derivatives of lupeol, α-amyrin and β-amyrin were detected at the phytochemistry analysis. HdCL did not alter the relative weight of organs, hematological parameters and volume of ascitic fluid recovered. In solid model, HdCL reduced (P < 0.05) paw volume, but did not altered thickness, paw weight and histological parameters. S180sol induced necrosis, metastasis and destruction of bone, cartilage and muscles. Bleeding, vessel congestion and oncocytes were observed in PLN. In paw, HdCL did not alter FoxP3 and HSP-60 expressions but reduced the CD4 and CD8 expressions, while at PLN, HdCL reduced the expressions of all markers. HdCL decreased (P < 0.05) serum levels of malondialdehyde in ascitic model.
Treatment with HdCL reduced oxidative damage and modulated the expressions of CD4, CD8, FoxP3and HSP-60 in S180 solid tumor model, which can be associated to the presence of triterpenes, such as α-amyrin, β-amyrin and lupeol cinnamate. Present data emphasizes the importance of immune system in cancer and highlights the evaluation of the pharmacological properties of plants used by population as phytoterapics.
在巴西，希马坦图斯·德拉西库斯的乳胶被用于治疗炎症、伤口愈合和癌症。本研究评估了希马坦图斯·德拉西库斯乳胶（HdCL）在肉瘤 180 荷瘤小鼠（S180）中的抗肿瘤潜力。
HdCL 是在巴西 Crato-CE 获得的。进行了定性植物化学物质分析、核磁共振（NMR）和微生物分析。瑞士小鼠根据肿瘤类型分为六组：1）腹水模型，GI（对照；0.9%生理盐水）、GII（Sasc）和 GIII（Sasc/HdCL/14 天）；2）实体瘤模型，GIV（对照；0.9%生理盐水）、GV（Ssol）和 GVI（Ssol/HdCL/10 天）。HdCL 和 0.9%生理盐水以 0.2 mL、SID 的剂量通过灌胃给药，持续 10 或 14 天。对于腹水模型，将 0.5 mL 的 S180 悬浮液（4×10 个细胞/mL）腹膜内接种，对于实体瘤模型，将细胞皮下接种（25 µL）在小鼠右后爪上。采集血液样本以评估血液学和氧化应激。在实体瘤模型中，测量爪子的厚度、体积和重量。处死小鼠后，收集脾脏、肝脏和肾脏，以评估相对器官重量。用 H&E 和 CD4、CD8、HSP-60 和 Foxp3 免疫组织化学分析爪子和腘窝淋巴结（PLN）的组织片段。
HdCL 呈乳白色外观，粉红色上清液。在植物化学分析中检测到酚类、类黄酮、黄烷酮、游离甾体和齐墩果酸、α-香树脂醇和 β-香树脂醇的肉桂酰衍生物。HdCL 未改变器官的相对重量、血液学参数和腹水回收量。在实体瘤模型中，HdCL 降低了（P<0.05）爪子体积，但未改变厚度、爪子重量和组织学参数。S180sol 诱导了坏死、转移和骨、软骨和肌肉的破坏。在 PLN 中观察到出血、血管充血和肿瘤细胞。在爪子中，HdCL 不改变 FoxP3 和 HSP-60 的表达，但降低了 CD4 和 CD8 的表达，而在 PLN 中，HdCL 降低了所有标志物的表达。HdCL 降低了（P<0.05）腹水模型中丙二醛的血清水平。
HdCL 治疗降低了 S180 实体瘤模型中的氧化损伤，并调节了 CD4、CD8、FoxP3 和 HSP-60 的表达，这可能与 α-香树脂醇、β-香树脂醇和齐墩果酸肉桂酯等三萜类物质的存在有关。目前的数据强调了免疫系统在癌症中的重要性，并强调了评估人群用作植物疗法的植物的药理学特性。
