A synthetic curcumin derivative hydrazinobenzoylcurcumin induces autophagy in A549 lung cancer cells
A synthetic curcumin derivative hydrazinobenzoylcurcumin induces autophagy in A549 lung cancer cells
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DOI：
10.3109/13880209.2013.816971
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发表时间：
2014-01
影响因子：
3.8
通讯作者：
Guang‐Zhou Zhou;Shuai Zhang;Lu Zhang;Gangchun Sun;Xiao-Bing Chen
中科院分区：
文献类型：
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作者：
Guang‐Zhou Zhou;Shuai Zhang;Lu Zhang;Gangchun Sun;Xiao-Bing Chen
抽象上下文：姜黄素对多种癌细胞具有生长抑制活性，但生物利用度低限制了其在化疗试验中的应用。如今，已知越来越多的姜黄素衍生物或类似物，希望取代姜黄素并规避这一问题。肼基苯甲酰姜黄素（HBC）已被合成，并在以前的报告中被鉴定为有效的细胞增殖抑制剂。目的：探讨高胆红素血症（HBC）诱导人非小细胞肺癌（A549）细胞自噬的新机制。材料与方法：细胞培养后，用不同浓度（10-80 μM）的HBC处理不同时间（1-24 h）的细胞。显微镜下观察A549细胞的形态学变化及自噬溶酶体。吖啶橙子染色法检测自噬溶酶体，单丹酰尸胺（MDC）法检测自噬泡，GFP-LC 3转染法检测自噬泡。蛋白质印迹法用于评估微管相关蛋白轻链3（LC 3）的转化。结果如下：HBC可诱导A549细胞自噬溶酶体形成，并呈剂量和时间依赖性，80 μM HBC作用24 h后对A549细胞活力的抑制率达76.68 ± 5.81%。自噬泡呈浓度依赖性增加。此外，LC 3-I转化为LC 3-II，GFP标记的LC 3阳性细胞内空泡的积累以及自噬体与溶酶体的融合增加表明发生了自噬。结论：姜黄素衍生物诱导A549细胞自噬是一种新的细胞死亡机制。
Abstract Context: Curcumin exhibits growth-suppressive activity against a variety of cancer cells, but low bioavailability restricts its application in chemotherapeutic trials. Nowadays, a growing number of curcumin derivatives or analogs are known, hoping to replace curcumin and circumvent this problem. Hydrazinobenzoylcurcumin (HBC) has been synthesized and identified as a potent inhibitor of cell proliferation in previous reports. Objective: This study presents a novel mechanism of cell autophagy induced by HBC in the human non-small lung epithelial carcinoma (A549) cells. Materials and methods: Cells were cultured and treated with HBC at different concentrations (10–80 μM) and at different time periods (1–24 h). Microscopic analysis was used to detect the morphology changes and autophagolysosomes of A549 cells. An acridine orange staining assay was conducted to evaluate the autophagolysosomes and autophagic vacuoles was analyzed by monodansylcadaverine (MDC) and GFP-LC3 transfection analysis. Western blotting was used to assess the conversion of microtubule-associated protein light chain 3 (LC3). Results: HBC could induce A549 cells autophagolysosomes formation in a dose and time-dependent manner and the inhibitory rate of HBC (80 μM) on the viability of A549 cells reached 76.68 ± 5.81% after 24 h of treatment. Autophagic vacuoles increased in a concentration-dependent manner in HBC-treated cell. Furthermore, conversion of LC3-I to LC3-II, accumulation of GFP-tagged LC3 positive intracellular vacuoles and increased fusion of autophagosomes with lysosomes suggested the occurrence of autophagy. Conclusion: Our data indicate that HBC induced A549 cell autophagy, which is a novel cell death mechanism induced by curcumin derivatives.