Selective cytotoxic activity of the marine-derived batzelline compounds against pancreatic cancer cell lines
Selective cytotoxic activity of the marine-derived batzelline compounds against pancreatic cancer cell lines
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DOI：
10.1097/cad.0b013e32831fa39e
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发表时间：
2009-02-01
影响因子：
2.3
通讯作者：
Wright, Amy E.
中科院分区：
文献类型：
--
作者：
Guzman, Esther A.;Johnson, Jacob D.;Wright, Amy E.
胰腺癌是美国癌症死亡的第四大原因。这种疾病的预后是非常消极的，因为癌症通常会在患者出现症状时转移。虽然联合治疗显示出一些希望，但需要新的药物来治疗这种疾病。鉴于我们对寻找胰腺癌新疗法的兴趣，我们试图确定batzellines的已知细胞毒性活性是否延伸到胰腺癌细胞系。batzellines是从深水加勒比海海绵Batzelle sp（Esperiopsidae科，Poecilosclerida目）获得的吡咯亚氨基醌生物碱。我们在这里表明，batzellines表现出选择性细胞毒性对胰腺癌细胞系AsPC-1，Panc-1，BxPC-3，和MIA PaCa 2相比，正常的非洲绿色猴肾上皮细胞系Vero。batzellines通过诱导细胞周期停滞引起细胞毒性，所述细胞周期停滞由其嵌入DNA和/或抑制拓扑异构酶11活性的能力介导。isobatzellines A和C对胰腺癌细胞系的细胞毒性能力，它们对正常细胞的低毒性，以及它们报道的合成能力，使它们成为具有潜在化疗作用的有趣化合物，可能值得进一步研究。抗癌药物20：149-155（C）2009年沃尔特斯·克鲁沃健康垂直栏利平科特威廉姆斯&威尔金斯。
Pancreatic cancer is the fourth leading cause of cancer death in the United States. The prognosis of the disease is very negative, because the cancer will be usually metastasized by the time a patient manifests symptoms. Although combination therapy shows some promise, new drugs to treat the disease are needed. Given our Interest in finding new therapies for pancreatic cancer, we sought to determine whether the known cytotoxic activity of the batzellines extended to pancreatic cancer cell lines. The batzellines are pyrroloiminoquinones alkaloids obtained from the deep-water Caribbean sponge Batzelle sp (family Esperiopsidae, order Poecilosclerida). We show here that batzellines exhibit selective cytotoxicity towards the pancreatic cancer cell lines AsPC-1, Panc-1, BxPC-3, and MIA PaCa2 compared with the normal African green monkey kidney epithelial cell line Vero. The batzellines cause cytotoxicity by inducing cell cycle arrest that is mediated by their ability to intercalate into DNA and/or inhibit topoisomerase 11 activity. The cytotoxic abilities of isobatzellines A and C against pancreatic cancer cell lines, their low toxicity against normal cells, and their reported ability to be synthesized makes them interesting compounds with potential chemotherapeutic effects that may merit further research. Anti-Cancer Drugs 20:149-155 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.