铁诱导肿瘤细胞自杀

Iron Induces Death In Tumor Cells

 

　

日期:2009年3月13日

资料来源:德国研究中心Helmholtz协会。

　

　

肿瘤细胞和健康细胞在代谢强度上有显著差异。科学家们已经利用了这一差异;通过释放细胞铁，它们能够选择性地诱导肿瘤细胞死亡。

　

　

　

癌细胞的快速生长及其频繁的分裂有其代价:癌细胞需要比健康细胞多得多的能量。它们的新陈代谢以全速运转，需要大量的微量元素，尤其是铁元素。然而，细胞中的铁含量过高会导致极端有害的自由基的产生。

 

为了保护自身不受这些物质的影响，细胞通过将游离铁与被称为铁储存蛋白的物质结合在一起。

 

与曼海姆大学医院皮肤科医生、卡斯滕·古洛博士和DKFZ免疫遗传学部门负责人Peter Krammer教授合作，研究了Sezary的疾病(也称为Sezary综合征)，这是一种极具侵袭性的皮肤T细胞淋巴瘤。大多数现有的治疗方法对这种致命的癌症并不是很有效。

 

利用分子生物学技巧，Gulow和他的同事成功阻止了淋巴瘤细胞中一个铁储存蛋白的产生。这导致了这些细胞中游离的、不受束缚的铁含量的上升。铁能促进氧自由基的产生，从而导致氧化应激，从而对癌细胞造成损害并导致死亡。然而，健康细胞的铁含量较低，却能安然无恙地存活下来。

　

 

DKFZ的研究人员已经发现了这种铁效应在其他淋巴瘤中也起作用的证据。他们现在正在研究选择性释放铁是否适合发展一种新的癌症治疗方法。

　

　

 

Iron Induces Death In Tumor Cells

Date: March 13, 2009

Source: Helmholtz Association of German Research Centres

Summary:

Tumor cells and healthy cells differ considerably in metabolism intensity. Scientists have now taken advantage of this difference; by releasing cellular iron, they were able to induce death selectively in tumor cells.

FULL STORY

Rapid growth of cancer cells and their frequent divisions have their price: Cancer cells need considerably more energy than healthy cells. Their metabolism runs at full speed and requires large amounts of micronutrients, particularly iron. However, high levels of iron in the cell lead to the production of extremely harmful free radicals.

 

To protect itself from these, the cell inactivates free iron by binding it to what are called iron storage proteins.

Collaborating with physicians of the Dermatology Department of Mannheim University Hospitals, Dr. Karsten Gülow and Professor Dr. Peter Krammer, head of the Division of Immunogenetics at DKFZ, investigated Sézary's disease (also called Sézary syndrome), an extremely aggressive type of cutaneous T cell lymphoma. The majority of currently available treatments are not really effective against this fatal type of cancer.

Using a molecular-biological trick, Gülow and colleagues succeeded in blocking the production of one of the iron storage proteins in lymphoma cells. This leads to a rise in the level of free, non-bound iron in these cells. The iron boosts the production of free oxygen radicals which cause oxidative stress and, thus, cause damage to the cancer cells and induce their death. Healthy cells with their low iron level, however, survive the treatment unharmed.

The DKFZ researchers have already found evidence that this iron effect also works in other lymphomas. They are now investigating whether selective release of iron may be a suitable approach for developing a novel cancer treatment.

Michael K. Kiessling, Claus D. Klemke, Marcin M. Kamiński, Ioanna E. Galani, Peter H. Krammer, and Karsten Gülow: Inhibition of constitutively activated NF-κB induces ROS- and iron dependent cell death in cutaneous T cell lymphoma. Cancer Research 2009; DOI:10.1158/0008-5472.CAN-08-3221

The German Cancer Research Center is funded by the German Federal Ministry of Education and Research (90%) and the State of Baden-Württemberg (10%).

https://www.sciencedaily.com/releases/2009/03/090311103607.htm