Inhibitory Effects of Salinomycin on Cell Survival, Colony Growth, Migration, and Invasion of Human Non-Small Cell Lung Cancer A549 and LNM35: Involvement of NAG-1.
Inhibitory Effects of Salinomycin on Cell Survival, Colony Growth, Migration, and Invasion of Human Non-Small Cell Lung Cancer A549 and LNM35: Involvement of NAG-1.
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DOI：
10.1371/journal.pone.0066931
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Attoub S
中科院分区：
文献类型：
--
作者：
Arafat K;Iratni R;Takahashi T;Parekh K;Al Dhaheri Y;Adrian TE;Attoub S
肿瘤学家和药理学家面临的一个主要挑战是开发更有效和毒性更小的药物，以减少肿瘤生长并提高肺癌患者的生存率。盐霉素是一种聚醚类抗生素，用于杀死革兰氏阳性细菌，包括分枝杆菌、恶性疟原虫等原生动物和导致家禽球虫病的寄生虫。这种古老的药物现在是一种重要的抗癌候选药物，它选择性地抑制癌症干细胞的生长。我们研究了盐霉素对分化的人非小细胞肺癌细胞系LNM 35和A549的存活、集落生长、迁移和侵袭的影响。盐霉素通过半胱天冬酶3/7相关的细胞死亡途径引起LNM 35和A549细胞活力的浓度和时间依赖性降低。同样，盐霉素（2.5-5 µM，持续7天）显著降低了软琼脂中LNM 35和A549菌落的生长。转移是肺癌相关死亡的主要原因。在这种情况下，盐霉素诱导细胞迁移和侵袭的时间和浓度依赖性抑制。我们还首次证明盐霉素诱导促凋亡蛋白NAG-1的表达显著增加，从而抑制肺癌细胞侵袭，但不抑制细胞存活。这些发现确定盐霉素作为一种有前途的新型肺癌治疗药物。
A major challenge for oncologists and pharmacologists is to develop more potent and less toxic drugs that will decrease the tumor growth and improve the survival of lung cancer patients. Salinomycin is a polyether antibiotic used to kill gram-positive bacteria including mycobacteria, protozoans such as plasmodium falciparum, and the parasites responsible for the poultry disease coccidiosis. This old agent is now a serious anti-cancer drug candidate that selectively inhibits the growth of cancer stem cells. We investigated the impact of salinomycin on survival, colony growth, migration and invasion of the differentiated human non-small cell lung cancer lines LNM35 and A549. Salinomycin caused concentration- and time-dependent reduction in viability of LNM35 and A549 cells through a caspase 3/7-associated cell death pathway. Similarly, salinomycin (2.5–5 µM for 7 days) significantly decreased the growth of LNM35 and A549 colonies in soft agar. Metastasis is the main cause of death related to lung cancer. In this context, salinomycin induced a time- and concentration-dependent inhibition of cell migration and invasion. We also demonstrated for the first time that salinomycin induced a marked increase in the expression of the pro-apoptotic protein NAG-1 leading to the inhibition of lung cancer cell invasion but not cell survival. These findings identify salinomycin as a promising novel therapeutic agent for lung cancer.
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影响因子：
7.3
作者：
Kim, Ju-Hwa;Chae, Minji;Yoon, Sungpil
通讯作者：
Yoon, Sungpil
影响因子：
64.5
作者：
Gupta PB;Onder TT;Jiang G;Tao K;Kuperwasser C;Weinberg RA;Lander ES
通讯作者：
Lander ES
影响因子：
3
作者：
Huczynski, Adam
通讯作者：
Huczynski, Adam
DOI：
10.1073/pnas.1110431108
发表时间：
2011-08-09
影响因子：
11.1
作者：
Lu, Desheng;Choi, Michael Y.;Carson, Dennis A.
通讯作者：
Carson, Dennis A.
影响因子：
6.4
作者：
Oak, Prajakta S.;Kopp, Florian;Roidl, Andreas
通讯作者：
Roidl, Andreas