Laboratório de Farmacologia e Toxicologia Celular, Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia, Go, Brazil.
J Pharm Pharmacol. 2009 Dec;61(12):1709-14. doi: 10.1211/jpp/61.12.0017.
The antitumoural properties of grandisin, a tetrahydrofuran neolignan from Piper solmsianum, were investigated by in-vitro and in-vivo assays using the Ehrlich ascites tumoural (EAT) model.
Viability of the tumour cells was evaluated by Trypan blue exclusion and MTT methods, after incubation with grandisin (0.017-2.3 microm). The effects of grandisin on the activity of caspase-3, -6, -8, and -9 were also investigated using colorimetric protease kits. In-vivo studies were performed in EAT-bearing mice treated intraperitoneally with 2.5, 5 or 10 mg/kg grandisin for 10 days.
Grandisin inhibited the growth of EAT cells, by both methods, with IC50 values less than 0.25 microm. The results showed that the activity of all the caspases studied increased in grandisin-treated cells, when compared with control, non-treated cells. Administering grandisin to EAT-bearing mice increased survival of the animals, in a dose-dependent manner. Simultaneously, we detected a 66.35% reduction of intraperitoneal tumour cell burden in the animals treated with 10 mg/kg grandisin. Additionally, in these animals, the marked increase of vascular endothelial growth factor (VEGF) levels, induced by EAT development, was decreased with treatment with grandisin, resulting in a reduction of 32.1% of VEGF levels in the peritoneal washing supernatant, when compared with the control.
The results demonstrated that grandisin induced in-vitro cytotoxicity and antiangiogenic effects in mice while it acted against tumour evolution, prolonging host survival.
从 Piper solmsianum 中分离得到的四氢呋喃新木脂素 grandisin 通过体外和体内实验，利用艾氏腹水瘤（EAT）模型研究其抗肿瘤特性。
用台盼蓝排斥和 MTT 法检测肿瘤细胞活力，用 grandisin（0.017-2.3 μm）孵育细胞。还使用比色蛋白酶试剂盒研究了 grandisin 对 caspase-3、-6、-8 和 -9 活性的影响。体内研究在腹腔注射 2.5、5 或 10 mg/kg grandisin 10 天的 EAT 荷瘤小鼠中进行。
Grandisin 通过两种方法抑制 EAT 细胞生长，IC50 值均小于 0.25 μm。结果表明，与对照组相比，用 grandisin 处理的细胞中所有研究的半胱天冬酶活性均增加。向 EAT 荷瘤小鼠给予 grandisin 可剂量依赖性地增加动物的存活率。同时，我们检测到腹腔内肿瘤细胞负荷在给予 10 mg/kg grandisin 的动物中减少了 66.35%。此外，在这些动物中，由 EAT 发展引起的血管内皮生长因子（VEGF）水平的显著增加通过用 grandisin 处理而降低，导致腹腔冲洗上清液中的 VEGF 水平降低了 32.1%与对照组相比。
结果表明，grandisin 在体内诱导了细胞毒性和抗血管生成作用，同时抑制了肿瘤的发展，延长了宿主的存活。
