Zakaria Sherin, Helmy Maged Wasfy, Salahuddin Ahmed, Omran Gamal
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kaferelsheikh University, P.O. Box 33516, Kaferelsheikh, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt.
Biomed Pharmacother. 2018 Dec;108:65-75. doi: 10.1016/j.biopha.2018.09.016. Epub 2018 Sep 11.
Benzyl isothiocyanate (BITC) is a member of the isothiocyanate compounds that found in cruciferous vegetables. BITC has a potential anticancer effect in different types of tumors. Few studies referred to the antineoplastic effect of BITC against HCC. The mechanism of BITC concerning retardation of HCC progression is incompletely understood.
This study evaluated the role of HGF, pAkt and STAT3 in BITC induced HCC growth retardation.
HCC was induced in mice using diethylnitrosamine (DEN) 75 mg/kg once a week for 4 weeks. BITC 10 and 20 mg/kg was given to mice orally each day for 10 weeks. The HCC cell lines HepG2 and Huh-7 were also used to evaluate the effect of BITC on tumor cells behavior. Immunoassay was used to detect expressions of caspase-3 activity, VEGF, MMP-2, TNF-α, HGF and pAkt. STAT3 expression was detected in liver tissues using immunohistochemical staining.
BITC has a potential role in suppressing hepatic precancerous lesion progression in mice. The drug increased caspase-3 activity in tumor cells and inhibited the angiogenic marker VEGF. It also decreased the metastatic marker MMP-2. This anticancer effect of BITC was observed in DEN treated mice as well as in hepatoma cell lines. The reported antineoplastic activity was correlated with downregulation of HGF and its downstream molecules pAkt and STAT3.
The effect of BITC on HGF /pAkt/ STAT3 axis has a potential role in both chemopreventive and chemotherapeutic effects of BITC.
异硫氰酸苄酯（BITC）是十字花科蔬菜中发现的异硫氰酸酯化合物成员。BITC在不同类型肿瘤中具有潜在的抗癌作用。很少有研究提及BITC对肝癌的抗肿瘤作用。BITC延缓肝癌进展的机制尚不完全清楚。
本研究评估了HGF、pAkt和STAT3在BITC诱导的肝癌生长延缓中的作用。
使用二乙基亚硝胺（DEN）以75mg/kg的剂量每周一次给小鼠诱导肝癌，共4周。每天给小鼠口服10mg/kg和20mg/kg的BITC，持续10周。还使用肝癌细胞系HepG2和Huh-7评估BITC对肿瘤细胞行为的影响。采用免疫测定法检测caspase-3活性、VEGF、MMP-2、TNF-α、HGF和pAkt的表达。使用免疫组织化学染色检测肝组织中STAT3的表达。
BITC在抑制小鼠肝前病变进展方面具有潜在作用。该药物增加了肿瘤细胞中caspase-3的活性，并抑制血管生成标志物VEGF。它还降低了转移标志物MMP-2。在DEN处理的小鼠以及肝癌细胞系中均观察到BITC的这种抗癌作用。所报道的抗肿瘤活性与HGF及其下游分子pAkt和STAT3的下调相关。
BITC对HGF/pAkt/STAT3轴的作用在BITC的化学预防和化学治疗作用中均具有潜在作用。
