A novel activity from an old compound: Manzamine A reduces the metastatic potential of AsPC-1 pancreatic cancer cells and sensitizes them to TRAIL-induced apoptosis.
A novel activity from an old compound: Manzamine A reduces the metastatic potential of AsPC-1 pancreatic cancer cells and sensitizes them to TRAIL-induced apoptosis.
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DOI：
10.1007/s10637-010-9422-6
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发表时间：
2011-10
影响因子：
3.4
通讯作者：
Wright, Amy E.
中科院分区：
文献类型：
--
作者：
Guzman, Esther A.;Johnson, Jacob D.;Linley, Patricia A.;Gunasekera, Sarath E.;Wright, Amy E.
胰腺癌是美国癌症死亡的第四大原因，需要治疗这种疾病的新药。胰腺癌细胞是高度转移性的并且表现出对细胞凋亡的抗性。能够恢复对细胞凋亡的敏感性或减少转移的小分子将具有针对这种疾病的治疗潜力。Manzamine A是一种从海绵中分离的生物碱，被怀疑对丝裂原活化激酶激酶（MEK）具有抑制活性。因此，在胰腺癌细胞中研究了Manzamine A的作用。用不同浓度的Manzamine A处理AsPC-1细胞48 h，观察AsPC-1细胞的表型、细胞毒性、细胞侵袭力和凋亡敏感性。Manzamine A减少单个细胞的形成，废除细胞迁移，并恢复细胞对TRAIL诱导的AsPC-1细胞凋亡的敏感性。其作用机制仍不清楚，因为manzamine A不抑制MEK。Manzamine A似乎在阻断肿瘤细胞侵袭以及恢复癌细胞对体外细胞凋亡的易感性方面具有以前未被认识的活性，因此具有用作现有癌症疗法的佐剂的潜力。
Pancreatic cancer is the fourth leading cause of cancer death in the United States, and new drugs to treat the disease are needed. Pancreatic cancer cells are highly metastatic and exhibit resistance to apoptosis. Small molecules that can restore sensitivity to apoptosis or reduce metastasis would have therapeutic potential against this disease. Manzamine A is an alkaloid isolated from marine sponges that was suspected to have inhibitory activity against the mitogen activated kinase kinase (MEK). Because of this, the effects of Manzamine A were studied in pancreatic cancer cells. AsPC-1 cells were treated for 48 h in the presence of various concentrations of Manzamine A and their phenotype, cytotoxicity, cell invasion and susceptibility to apoptosis were observed. Manzamine A decreased single cell formation, abrogated cell migration and restored the susceptibility of the cells to TRAIL-induced apoptosis in AsPC-1 cells. Its mechanism of action remains unknown, as manzamine A does not inhibit MEK. Manzamine A appears to have a formerly unrecognized activity in blocking tumor cell invasion as well as in restoring cancer cell susceptibility to apoptosis in vitro and therefore has the potential to be used as an adjuvant to existing cancer therapies.
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影响因子：
11.2
作者：
Ougolkov, AV;Fernandez-Zapico, ME;Billadeau, DD
通讯作者：
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影响因子：
5.1
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影响因子：
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影响因子：
15
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影响因子：
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作者：
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