School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan.
Department of Chinese Medicine, E-Da Hospital, Kaohsiung, Taiwan.
Environ Toxicol. 2018 Nov;33(11):1097-1104. doi: 10.1002/tox.22581. Epub 2018 Jul 4.
Benzyl isothiocyanate (BITC), a member of isothiocyanates (ITCs), has been shown to induce cell death in many human cancer cells, but there is no further report to show BITC suppresses glioblastoma multiforme cells in vivo. In the present study, we investigate the effects of BITC on the inhibition of GBM 8401/luc2 cell generated tumor on athymic nude mice. We established a luciferase expressing stable clone named as GBM 8401/luc2. Thirty male mice were inoculated subcutaneously with GBM 8401/luc2 cells to generate xenograft tumor mice model. Group I was treated with 110 μL phosphate-buffered solution plus 10 μL dimethyl sulfoxide, Group II-III with BITC (5 or 10 μmol/100 μL/day, relatively). Mice were given oral treatment of BITC by gavage for 21 days. Results showed that BITC did not affect the body weights. After anesthetized, the photons emitted from mice tumor were detected with Xenogen IVIS imaging system 200 and higher dose of BITC have low total photon flux than that of lower dose of BITC. Results also showed that higher dose of BITC have low total tumor volumes and weights than that of low dose of BITC. Isolated tumors were investigated by immunohistochemical analysis and results showed that BITC at both dose of treatment weakly stained with anti-MCL1 and -XIAP. However, both dose of BITC treatments have strong signals of caspase-3 and Bax. Overall, these data demonstrated that BITC suppressed tumor properties in vivo. Overall, based on these observations, BITC can be used against human glioblastoma multiforme in the future.
苄基异硫氰酸酯(BITC)是异硫氰酸酯(ITC)的一种,已被证明可诱导多种人类癌细胞死亡,但尚无进一步的报告表明 BITC 能抑制体内多形性胶质母细胞瘤细胞。在本研究中,我们研究了 BITC 对荷瘤裸鼠中 GBM 8401/luc2 细胞生成肿瘤的抑制作用。我们建立了一个表达荧光素酶的稳定克隆,命名为 GBM 8401/luc2。30 只雄性小鼠皮下接种 GBM 8401/luc2 细胞,建立异种移植肿瘤小鼠模型。第 I 组给予 110 μL 磷酸盐缓冲液加 10 μL 二甲基亚砜,第 II-III 组给予 BITC(5 或 10 μmol/100 μL/天,相对)。通过灌胃给予小鼠口服 BITC 治疗 21 天。结果表明,BITC 不影响体重。麻醉后,用 Xenogen IVIS 成像系统 200 检测小鼠肿瘤发出的光子,高剂量 BITC 的总光子通量低于低剂量 BITC。结果还表明,高剂量 BITC 的总肿瘤体积和重量均低于低剂量 BITC。用免疫组化分析分离的肿瘤,结果表明,BITC 在两种剂量的治疗下均与抗 MCL1 和抗 XIAP 弱阳性染色。然而,两种剂量的 BITC 治疗均有强烈的 caspase-3 和 Bax 信号。总的来说,这些数据表明 BITC 抑制了体内肿瘤的特性。总的来说,基于这些观察结果,BITC 可在未来用于治疗人类多形性胶质母细胞瘤。