切断癌细胞的葡萄糖供应 启动癌细胞死亡之路-加州大学洛杉矶分校的研究发现

Starve cancer cells of sugar and they start to die. Sounds simple. You can do it a lab. But can you do it in your own body?

 

翻译:蓝山

 

加州大学洛杉矶分校(UCLA)的一项新研究表明,让癌细胞饥饿-癌细胞依赖糖来获取能量,而正常细胞只有在受到胁迫的情况下才会依赖糖来获取能量,从而引发了细胞死亡(细胞凋亡)的过程。引发细胞死亡是许多癌症治疗的目标。可以这么简单吗???

 

对酮类饮食的研究表明,高脂肪的生酮饮食会在应激中产生低血糖或低糖环境,并使癌细胞挨饿。同样的,一些研究表明,在化疗前的一天,当天和化疗后的一天,二天禁食可以提高癌症治疗的效率(死亡率)。禁食同样会产生一种叫做酮症的生理状态,也会产生一种糖的短缺,这种物质会对癌细胞产生压力,使它们更容易受到化疗的影响。

 

相反,我们知道糖尿病、糖尿病前期、代谢综合症和胰岛素抵抗的患者,持续高血糖的情况会导致更高的癌症发病率。底线:含糖的血液滋养癌细胞。

 

以下是一篇描述加州大学洛杉矶分校研究的文章摘录:

 

加州大学洛杉矶分校的研究显示,葡萄糖缺乏会激活杀死癌细胞的反馈回路。

 

 

与正常细胞相比,癌细胞对葡萄糖的胃口大得惊人,其结果是细胞新陈代谢的转变,即有氧糖酵解或“瓦博格效应。研究人员将注意力集中在癌症治疗的可能靶点上,研究了癌症细胞中的生化信号如何调节新陈代谢状态。

 

现在,在一项独特的研究中,由分子和医学药理学教授Thomas Graeber领导的加州大学洛杉矶分校的研究小组,研究了相反的方面:葡萄糖的代谢如何影响癌细胞中存在的生化信号。

 

2012626日发表的研究,在《分子系统生物学,格雷柏和他的同事们证明葡萄糖饥饿——也就是说,剥夺癌细胞获取糖激活葡萄糖代谢和信号放大回路,导致癌细胞死亡的有毒活性氧积累,破坏细胞分子和离子,这些是抗氧化剂如维生素C的靶向的目标。

 

包括加州大学洛杉矶分校的科学家们嘎吱声研究所分子成像、分子医学研究所,加州纳米系统研究所Jonsson综合癌症中心,以利并广泛再生医学和干细胞研究中心,和医学、病理学和实验室的研究演示了在揭示代谢和信号在网络层之间的关系中系统生物学的力量。

 

为了解释这种看似矛盾的结果,即葡萄糖剥夺降低了生存能力,同时增加了信号转导,作者使用了一种无偏的系统-生物学方法,包括磷-酪氨酸质谱和其他生化分析技术。

 

通过对代谢和信号之间的“串扰”的评估,他们发现葡萄糖的缺乏激活了一个正反馈回路,葡萄糖的剥夺诱导了活性氧的增加,从而抑制酪氨酸信号的负调控。由此产生的酪氨酸磷酸化的超生理水平会产生额外的活性氧。

 

GRAEBER解释说:“因为癌细胞生长在新陈代谢的边缘,所以这种氧化应激的放大循环最终会压垮并杀死癌细胞。”“这些发现说明了新陈代谢和维持癌症细胞内稳态的信号之间的微妙平衡。

 

此外,作者还展示了利用这种正反馈环进行治疗干预的可能性。将短期的葡萄糖剥夺与酪氨酸磷酸酶抑制剂结合,在癌细胞系中表现出协同性细胞死亡。

 

“了解新陈代谢和信号传递之间的联系,将会赋予新的治疗方法来诱导这一新陈代谢灾难,”Graham说。

https://s.click.taobao.com/xJt8MNw

 

参考文献

Starve cancer cells of sugar and they start to die. Sounds simple. You can do it a lab. But can you do it in your own body?

 

A new study from UCLA demonstrates that starving cancer cells, which rely on sugar for energy, unlike normal cells which rely upon sugar for energy only when they are under duress, initiates a process leading to cell death (apoptosis). Triggering cell death  is the goal of many cancer treatments. Could it be this simple????

 

Studies on ketongenic diets  show that a high fat ketogenic diet that produces a low glycemic or low sugar environment in the will stress and starve cancer cells. Similarly, some research has shown that fasting a day before, the day of and a day or two after chemotherapy improves the effectiveness (kill rate) of the cancer treatment. Fasting similarly produces a physiologic state called ketosis and a shortage of sugars for fuel which stresses cancer cells and makes them more vulnerable to chemotherapy effects.

 

Conversely we know that patients with diabetes, pre-diabetes, metabolic syndrome and insulin resistance..conditions of persistent high blood sugar suffer higher rates of cancer.  Botton Line: Sugary blood feeds cancer cells.

 

Here is an excerpt of an article that describes the UCLA Study:

Glucose deprivation activates feedback loop that kills cancer cells, UCLA study shows

 

By Jennifer Marcus

 

Compared to normal cells, cancer cells have a prodigious appetite for glucose, the result of a shift in cell metabolism known as aerobic glycolysis or the “Warburg effect.” Researchers focusing on this effect as a possible target for cancer therapies have examined how biochemical signals present in cancer cells regulate the altered metabolic state.

 

Now, in a unique study, a UCLA research team led by Thomas Graeber, a professor of molecular and medical pharmacology, has investigated the reverse aspect: how the metabolism of glucose affects the biochemical signals present in cancer cells.

 

In research published June 26, 2012 in the journal Molecular Systems Biology, Graeber and his colleagues demonstrate that glucose starvation — that is, depriving cancer cells of glucose —activates a metabolic and signaling amplification loop that leads to cancer cell death as a result of the toxic accumulation of reactive oxygen species, the cell-damaging molecules and ions targeted by antioxidants like vitamin C.

 

The research, which involved UCLA scientists from the Crump Institute for Molecular Imaging, the Institute for Molecular Medicine, the California NanoSystems Institute, the Jonsson Comprehensive Cancer Center, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and the Department of Pathology and Laboratory Medicine, demonstrates the power of systems biology in uncovering relationships between metabolism and signaling at the network level.

 

To explain the seemingly contradictory result that glucose deprivation reduced viability and at the same time increased signaling, the authors used an unbiased systems-biology approach that included phospho-tyrosine mass spectrometry and other biochemical profiling techniques.

 

Assessing the “crosstalk” between metabolism and signaling, they discovered that the glucose deprivation activates a positive feedback loop whereby the withdrawal of glucose induces increased levels of reactive oxygen species, which in turn inhibit negative regulators of tyrosine signaling. The resulting supra-physiological levels of tyrosine phosphorylation then generate additional reactive oxygen species.

 

BECAUSE CANCER CELLS LIVE ON THE EDGE OF WHAT IS METABOLICALLY FEASIBLE, THIS AMPLIFYING CYCLE OF OXIDATIVE STRESS ULTIMATELY OVERWHELMS AND KILLS THE CANCER CELL,” GRAEBER EXPLAINED. “THESE FINDINGS ILLUSTRATE THE DELICATE BALANCE THAT EXISTS BETWEEN METABOLISM AND SIGNALING IN THE MAINTENANCE OF CANCER CELL HOMEOSTASIS.”

 

In addition, the authors showed the possibility of exploiting this positive feedback loop for therapeutic intervention. Combining short-term glucose deprivation with an inhibitor of tyrosine phosphatases, they demonstrated synergistic cell death in a cancer cell line.

 

Understanding the links between metabolism and signaling will empower new therapeutic approaches toward inducing this metabolic catastrophe,” Graham said.

http://www.integrativecanceranswers.com/killing-cancer-cells-by-starving-them-of-sugar/