Involvement of autophagy inhibition in Brucea javanica oil emulsion-induced colon cancer cell death.
Involvement of autophagy inhibition in Brucea javanica oil emulsion-induced colon cancer cell death.
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DOI：
10.3892/ol.2015.2875
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发表时间：
2015-03
期刊：
影响因子：
2.9
通讯作者：
Guo GF
中科院分区：
文献类型：
--
作者：
Yan Z;Zhang B;Huang Y;Qiu H;Chen P;Guo GF
鸦胆子油乳剂（BJOE）是B的石油醚提取物。爪哇胡椒是一种磷脂乳化的抗癌药物，在我国被广泛应用。B. javanica通过各种机制诱导癌细胞死亡;然而，不知道这些机制是否涉及自噬，自噬是癌症发展和治疗中重要过程。因此，本研究旨在研究BJOE是否调节HCT 116人结肠癌细胞中的自噬，以及自噬的调节是否是BJOE的抗癌机制。采用免疫印迹法分析暴露于BJOE后HCT 116癌细胞中微管相关蛋白轻链3（LC 3）（自噬的特异性蛋白标志物）的蛋白表达水平。通过Annexin V-异硫氰酸荧光素/碘化丙啶测定法检测HCT 116癌细胞的凋亡率。根据BJOE给药对HCT 116癌细胞中自噬的影响（诱导或抑制），应用功能相反的试剂（自噬抑制剂或诱导剂）来抵消这种影响，并再次检测癌细胞的凋亡率。自噬的作用（促存活或促死亡）通过比较抵消作用之前和之后的凋亡癌细胞的比率来证明。结果表明，BJOE抑制LC 3的蛋白表达水平，包括LC 3-I和LC 3-II形式，并诱导具有高水平基础LC 3的HCT 116癌细胞的凋亡。当通过施用海藻糖（一种自噬诱导剂）诱导自噬时，BJOE的自噬诱导活性显著减弱。这些数据表明，自噬抑制参与BJOE诱导的癌细胞死亡，并且这种抑制可能是BJOE的潜在抗癌机制。
Brucea javanica oil emulsion (BJOE), the petroleum ether extract of B. javanica emulsified by phospholipid, is widely used in China as an anticancer agent. The extracts from B. javanica induce cancer cell death by various mechanisms; however, it is not known whether these mechanisms involve autophagy, which is an important process in cancer development and treatment. Thus, the current study aimed to investigate whether BJOE modulates autophagy in HCT116 human colon cancer cells and whether modulation of autophagy is an anticancer mechanism of BJOE. Immunoblotting was employed to analyze the protein expression levels of microtubule-associated protein light-chain 3 (LC3), a specific protein marker of autophagy, in HCT116 cancer cells following exposure to BJOE. The apoptosis rate of the HCT116 cancer cells was detected by performing an Annexin V-fluorescein isothiocyanate/propidium iodide assay. According to the effect of BJOE administration on autophagy in the HCT116 cancer cells (induction or suppression), a functionally opposite agent (autophagy suppressor or inducer) was applied to counteract this effect, and the apoptosis rate of the cancer cells was detected again. The role of autophagy (pro-survival or pro-death) was demonstrated by comparing the rates of apoptotic cancer cells prior to and following the counteraction. The results revealed that BJOE suppressed the protein expression levels of LC3, including the LC3-I and LC3-II forms, and induced apoptosis in the HCT116 cancer cells with a high level of basal LC3. The apoptosis-inducing activity of BJOE was significantly attenuated when autophagy was induced by the administration of trehalose, an autophagy inducer. The data indicates that autophagy inhibition is involved in BJOE-induced cancer cell death, and that this inhibition may be a potential anticancer mechanism of BJOE.
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DOI：
10.1074/jbc.m110.138958
发表时间：
2011-04-15
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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作者：
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作者：
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