Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok Thailand.
Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand; Excellent Center for Drug Discovery (ECDD), Mahidol University, Bangkok, Thailand.
J Ethnopharmacol. 2018 Sep 15;223:10-21. doi: 10.1016/j.jep.2018.05.016. Epub 2018 May 17.
Plant materials used in this study were selected based on the ethnobotanical literature. Plants have either been utilized by Thai practitioners as alternative treatments for cancer or identified to exhibit anti-cancer properties.
To screen ethnomedicinal plants using a yeast cell-based assay for synthetic lethal interactions with cells deleted for RAD1, the yeast homologue of human ERCC4 (XPF) MATERIALS AND METHODS: Ethanolic extracts from thirty-two species of medicinal plants utilized in Thai traditional medicine were screened for synthetic lethal/sick interactions using a yeast cell-based assay. Cell growth was compared between the parental strain and rad1∆ yeast following exposure to select for specific toxicity of plant extracts. Candidate extracts were further examined for the mode of action using genetic and biochemical approaches.
Screening a library of ethanolic extracts from medicinal plants identified Bacopa monnieri and Colubrina asiatica as having synthetic lethal effects in the rad1∆ cells but not the parental strain. Synthetic lethal effects for B. monneiri extracts were more apparent and this plant was examined further. Genetic analysis indicates that pro-oxidant activities and defective excision repair pathways do not significantly contribute to enhanced sensitivity to B. monneiri extracts. Exposure to B. monneiri extracts resulted in nuclear fragmentation and elevated levels of ethidium bromide staining in rad1∆ yeast suggesting promotion of an apoptosis-like event. Growth inhibition also observed in the human Caco-2 cell line suggesting the effects of B. monnieri extracts on both yeast and human cells may be similar.
B. monneiri extracts may have utility in treatment of colorectal cancers that exhibit deficiency in ERCC4 (XPF).
本研究中使用的植物材料是根据民族植物学文献选择的。这些植物要么被泰国从业者用作癌症的替代治疗方法，要么被鉴定为具有抗癌特性。
使用基于酵母细胞的测定法筛选民族药用植物，以鉴定与人类 ERCC4（XPF）同源物 RAD1 缺失的细胞具有合成致死相互作用的植物。
使用基于酵母细胞的测定法筛选来自泰国传统医学中使用的 32 种药用植物的乙醇提取物，以鉴定合成致死/病态相互作用。在暴露于选择特定植物提取物毒性的情况下，比较亲本菌株和 rad1∆酵母之间的细胞生长。候选提取物进一步使用遗传和生化方法检查作用模式。
筛选药用植物乙醇提取物文库，鉴定出假马齿苋和亚洲长春花具有在 rad1∆细胞中具有合成致死作用，但在亲本菌株中没有。假马齿苋提取物的合成致死作用更为明显，因此进一步研究了这种植物。遗传分析表明，促氧化剂活性和有缺陷的切除修复途径对增强对假马齿苋提取物的敏感性没有显著贡献。暴露于假马齿苋提取物导致 rad1∆酵母中的核碎裂和溴化乙锭染色水平升高，表明促进类似凋亡的事件。在人 Caco-2 细胞系中也观察到生长抑制，这表明假马齿苋提取物对酵母和人类细胞的影响可能相似。
假马齿苋提取物可能对 ERCC4（XPF）缺失的结直肠癌治疗有用。
