Activity of mangosteen xanthones and teleocidin A-2 in death-receptor expression enhancement and tumor necrosis-factor related apoptosis-inducing ligand assays
Activity of mangosteen xanthones and teleocidin A-2 in death-receptor expression enhancement and tumor necrosis-factor related apoptosis-inducing ligand assays
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山竹xanthones和teleocidin A-2在死亡受体表达增强和肿瘤坏死因子相关凋亡诱导配体测定中的活性
DOI：
10.1021/np900404e
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
M.
中科院分区：
文献类型：
--
作者：
Kikuchi;H.; Ohtsuki;T.; Koyano;T.; Kowithayakorn;T.; Sakai;T.; Ishibashi;M.
进行了一项筛选研究，使用荧光素酶测定来鉴定增强死亡受体 5 (DR5) 表达的天然产物，并在生物测定指导下对两种生物体（山竹）的果皮和放线菌 CKK609 菌株进行分离，从而分离出八种氧杂蒽酮衍生物 (1−8) 和 teleocidin A-2 (9)。其中，化合物1、2和5是从G中分离得到的。来自放线菌的 mangostana 和 9 显示出有效的 DR5 启动子活性。此外，我们发现，联合使用加坦宁 (5) 和肿瘤坏死因子 (TNF) 相关凋亡诱导配体 (TRAIL) 对 TRAIL 耐药的人胃腺癌细胞 (AGS) 细胞具有增强作用。因此，目前的结果表明5具有通过上调DR5来克服TRAIL抗性的能力，并且可能是TRAIL抗性细胞的有效敏化剂。
A screening study using a luciferase assay to identify natural products that enhance death receptor 5 (DR5) expression was carried out, and bioassay-guided fractionation of two organisms, the pericarp ofGarcinia mangostana(mangosteen) and actinomycete CKK609 strain, led to the isolation of eight xanthone derivatives (1−8) and teleocidin A-2 (9). Among them, compounds1,2, and5, isolated fromG. mangostana, and9, from the actinomycete, showed potent DR5 promoter activity. Furthermore, we revealed that combined treatment with gartanin (5) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) showed a potentiation effect in sensitizing TRAIL-resistant human gastric adenocarcinoma (AGS) cells. Thus, the present results suggested that5has the ability to overcome TRAIL resistance via the up-regulation of DR5 and may be an effective sensitizer of TRAIL-resistant cells.