Withaferin A inhibits Epithelial to Mesenchymal Transition in Non-Small Cell Lung Cancer Cells.
Withaferin A inhibits Epithelial to Mesenchymal Transition in Non-Small Cell Lung Cancer Cells.
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DOI：
10.1038/s41598-018-34018-1
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发表时间：
2018-10-24
影响因子：
4.6
通讯作者：
Gupta RC
中科院分区：
文献类型：
--
作者：
Kyakulaga AH;Aqil F;Munagala R;Gupta RC
肺癌是全世界和美国癌症相关死亡的主要原因。尽管最近在治疗方法方面取得了进展，但转移仍然是肺癌的主要治疗挑战，并解释了极差的预后。上皮细胞向间质细胞转化（EMT）是一个复杂的细胞重编程过程，在非小细胞肺癌（NSCLC）的转移过程中起着重要作用，已成为一个有吸引力的药物靶点。在本研究中，我们研究了醉茄素A（WFA）（一种植物源性甾体内酯）对人非小细胞肺癌细胞系EMT的影响。首先，我们证明了WFA对A549和H1299 NSCLC细胞的细胞毒性具有时间和浓度依赖性。然后，将细胞暴露于≤ 0.5 µM WFA ≤ 4 h，以使细胞毒性最小化，并确定其对EMT、细胞粘附、运动、迁移和侵袭的影响。通过在含有TGFβ1（5 ng/mL）和TNFα（25 ng/mL）的无血清培养基中培养细胞48 h进行EMT诱导。我们观察到用WFA预处理细胞抑制A549和H1299细胞的细胞粘附、迁移和侵袭。通过免疫印迹、免疫荧光和qRT-PCR分析，我们证明WFA抑制了TGFβ1和TNFα诱导的两种细胞系中的EMT。WFA抑制A549和H1299细胞中Smad 2/3和NF-κB的磷酸化和核转位。总之，我们的研究提供了额外的证据，证明了WFA对NSCLC细胞中EMT诱导的抑制作用，并进一步证明了WFA对NSCLC转移的治疗潜力。
Lung cancer is the leading cause of cancer-related deaths worldwide and in the United States. Despite recent advancements in treatment approaches, metastasis remains a major therapeutic challenge in lung cancer and explains the extremely poor prognosis. Epithelial to mesenchymal transition (EMT), a complex process of cellular reprogramming has become an attractive drug target because it plays a crucial role in the metastasis of non-small cell lung cancer (NSCLC). In the present study, we examined the effects of withaferin A (WFA), a plant-derived steroidal lactone on EMT in human NSCLC cell lines. First, we demonstrated that WFA displayed time- and concentration-dependent cytotoxicity on A549 and H1299 NSCLC cells. Then, cells were exposed to ≤ 0.5 µM WFA for ≤ 4 h to minimize cytotoxicity and determined its effects on EMT, cell adhesion, motility, migration, and invasion. EMT induction was performed by culturing cells in serum-free media containing TGFβ1 (5 ng/mL) and TNFα (25 ng/mL) for 48 h. We observed that pretreatment of cells with WFA inhibited cell adhesion, migration, and invasion of A549 and H1299 cells. Using western blot, immunofluorescence, and qRT-PCR analysis, we demonstrated that WFA suppressed TGFβ1 and TNFα-induced EMT in both cell lines. Mechanistically, WFA suppressed the phosphorylation and nuclear translocation of Smad2/3 and NF-κB in A549 and H1299 cells. Together, our study provides additional evidence demonstrating the inhibitory effects of WFA on EMT induction in NSCLC cells and further demonstrates the therapeutic potential of WFA against the metastasis in NSCLC.
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影响因子：
7.3
作者：
Gonzalez DM;Medici D
通讯作者：
Medici D
影响因子：
3.7
作者：
Kumar M;Allison DF;Baranova NN;Wamsley JJ;Katz AJ;Bekiranov S;Jones DR;Mayo MW
通讯作者：
Mayo MW
DOI：
10.1016/j.bbrc.2012.06.047
发表时间：
2012-07-13
影响因子：
3.1
作者：
Kakar, Sham S.;Jala, Venkatakrishna R.;Fong, Miranda Y.
通讯作者：
Fong, Miranda Y.
影响因子：
9.7
作者：
Aqil, Farrukh;Jeyabalan, Jeyaprakash;Kausar, Hina;Bansal, Shyam S.;Sharma, Ram J.;Singh, Inder P.;Vadhanam, Manicka V.;Gupta, Ramesh C.
通讯作者：
Gupta, Ramesh C.
影响因子：
4.8
作者：
Kaileh, Mary;Vanden Berghe, Wim;Haegeman, Guy
通讯作者：
Haegeman, Guy