Marsdenia tenacissima extract induces apoptosis and suppresses autophagy through ERK activation in lung cancer cells.
Marsdenia tenacissima extract induces apoptosis and suppresses autophagy through ERK activation in lung cancer cells.
复制标题
通关藤提取物通过激活ERK诱导肺癌细胞凋亡并抑制自噬。
DOI：
10.1186/s12935-018-0646-4
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发表时间：
2018
影响因子：
5.8
通讯作者：
Li PP
中科院分区：
文献类型：
--
作者：
Jiao YN;Wu LN;Xue D;Liu XJ;Tian ZH;Jiang ST;Han SY;Li PP
马尾草是一种用于治疗恶性疾病几十年的草药。M. tenacissima提取物（MTE）对非小细胞肺癌（NSCLC）细胞具有显著的抗增殖活性，但其作用机制尚不清楚。在本研究中，我们探索了MTE在非小细胞肺癌细胞中与凋亡和自噬相关的潜在抗增殖机制，这两种机制是控制癌细胞生存和死亡的两种关键形式。MTT法观察H1975和A549细胞的增殖情况。Annexin V、PI染色、Caspase 3表达及活性检测细胞凋亡情况。Western blot检测自噬通量蛋白的表达。共聚焦显微镜观察内源性LC3-II斑点和LysoTracker染色。吖啶橙染色检测自噬液泡的形成。ERK是参与细胞自噬和凋亡的重要分子。在MEK/ERK抑制剂U0126存在的情况下，研究ERK对MTE影响的细胞凋亡和自噬的作用。MTE对非小细胞肺癌细胞有明显的生长抑制和诱导凋亡作用。MTE诱导的细胞凋亡与Caspase 3活性升高并存。MTE还通过上调LC3-II和p62的表达来损害自噬通量。自噬诱导剂EBSS不能消除MTE对自噬通量的损害，而自噬抑制剂Baf A1的存在使其增强。MTE通过影响溶酶体功能来阻断自噬体与溶酶体的融合，表现为LAMP1和Cathepsin b的表达降低。MTE处理后ERK分子变得超激活，但MEK/ERK抑制剂U0126消除了MTE引起的自噬抑制和细胞凋亡诱导，提示ERK信号通路部分参与了MTE导致的细胞死亡。我们的研究结果表明，MTE可诱导非小细胞肺癌细胞凋亡并抑制自噬。活化的ERK与MTE治疗后NSCLC细胞凋亡和自噬细胞死亡部分相关。本研究结果揭示了MTE抗NSCLC肿瘤活性的新机制。本文的在线版本（10.1186/s12935-018-0646-4）包含补充材料，授权用户可使用。
Marsdenia tenacissima is an herb medicine which has been utilized to treat malignant diseases for decades. The M. tenacissima extract (MTE) shows significant anti-proliferation activity against non-small cell lung cancer (NSCLC) cells, but the underlying mechanisms remain unclear. In this study, we explored the potential anti-proliferation mechanisms of MTE in NSCLC cells in relation to apoptosis as well as autophagy, which are two critical forms to control cancer cell survival and death. The proliferation of H1975 and A549 cells was evaluated by MTT assay. Cell apoptosis was assessed by Annexin V and PI staining, Caspase 3 expression and activity. Autophagy flux proteins were detected by Western blot with or without autophagy inducer and inhibitor. Endogenous LC3-II puncta and LysoTracker staining were monitored by confocal microscopy. The formation of autophagic vacuoles was measured by acridine orange staining. ERK is a crucial molecule to interplay with cell autophagy and apoptosis. The role of ERK on cell apoptosis and autophagy influenced by MTE was determined in the presence of MEK/ERK inhibitor U0126. The significant growth inhibition and apoptosis induction were observed in MTE treated NSCLC cells. MTE induced cell apoptosis coexisted with elevated Caspase 3 activity. MTE also impaired autophagic flux by upregulated LC3-II and p62 expression. Autophagy inducer EBSS could not abolish the impaired autophagic flux by MTE, while it was augmented in the presence of autophagy inhibitor Baf A1. The autophagosome–lysosome fusion was blocked by MTE via affecting lysosome function as evidenced by decreased expression of LAMP1 and Cathepsin B. The molecule ERK became hyperactivated after MTE treatment, but the MEK/ERK inhibitor U0126 abrogated autophagy inhibition and apoptosis induction caused by MTE, suggested that ERK signaling pathways partially contributed to cell death caused by MTE. Our results demonstrate that MTE caused apoptosis induction as well as autophagy inhibition in NSCLC cells. The activated ERK is partially associated with NSCLC apoptotic and autophagic cell death in response to MTE treatment. The present findings reveal new mechanisms for the anti-tumor activity of MTE against NSCLC. The online version of this article (10.1186/s12935-018-0646-4) contains supplementary material, which is available to authorized users.
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影响因子：
4.6
作者：
El Hasasna H;Athamneh K;Al Samri H;Karuvantevida N;Al Dhaheri Y;Hisaindee S;Ramadan G;Al Tamimi N;AbuQamar S;Eid A;Iratni R
通讯作者：
Iratni R
影响因子：
2.6
作者：
Ali, A.;Goffin, J. R.;Ellis, P. M.
通讯作者：
Ellis, P. M.
影响因子：
13.3
作者：
Kaminskyy, Vitaliy O.;Piskunova, Tatiana;Zhivotovsky, Boris
通讯作者：
Zhivotovsky, Boris
DOI：
10.4137/jcd.s11034
发表时间：
2013
期刊：
Journal of cell death
影响因子：
--
作者：
El-Khattouti A;Selimovic D;Haikel Y;Hassan M
通讯作者：
Hassan M
影响因子：
5.6
作者：
Liu G;Pei F;Yang F;Li L;Amin AD;Liu S;Buchan JR;Cho WC
通讯作者：
Cho WC