两年过去了,加拿大研究人员进行了一项有关一种药物的重要的研究,该药物能够摧毁癌细胞而不损害健康组织。这种物质被称为DCA(二氯乙酸),以NaDCA(二氯乙酸钠)的形式溶解在水中使用。
该药物目前正在加拿大艾伯塔大学进行的二期临床试验(人体患者)中。官方的DCA网站位于这里。
除了显而易见的拯救人类生命的机会外,这项研究提供了有关癌症运作方式的有趣解释。科学家们建议,大多数癌症并非具有遗传基础,而更可能是代谢性的。而且这是一种早已发现并已经使用了很久的疾病,具有已知的副作用。
要理解这个想法的简单性,需要了解一些细胞呼吸的细节。
我们体内的每个活细胞都需要能量来维持其生命活动。这种能量来自于消化过的食物,以葡萄糖分子的形式传递到细胞中。在细胞呼吸过程中,储存在葡萄糖化学键中的能量被转移到ATP分子(三磷酸腺苷)中。
除了作为一种潜在的救命药物外,DCA 还具有科学吸引力,因为它提供了对许多不同癌症内部机制的单一解释。换句话说,它表明癌症是一种代谢性疾病而非基因性疾病。
为了理解这一点,让我们将其放在细胞呼吸的大背景中。
我们体内的每个活细胞都需要以适合燃料必要的生化反应的形式产生能量。能量转换的过程称为细胞呼吸,其目标是将能量储存在 ATP 分子中。
最初的能量来自消化食物,以葡萄糖分子的形式到达细胞,这里开始呼吸。
许多癌细胞的呼吸在糖酵解阶段停止,因为它们的线粒体受到抑制线粒体门控酶丙酮酸脱氢酶(PDH)的抑制作用。与基于线粒体的葡萄糖氧化相比,糖酵解在能量生产方面效率较低,细胞必须使用更多葡萄糖来维持其生命。这种更高的葡萄糖摄取实际上在氟代脱氧葡萄糖正电子发射断层扫描(FDG-PET)中得到利用,这种扫描常用于癌症检测。
失去功能的线粒体具有超极化的内膜,这种电静电势的积累使细胞的凋亡剂局限于线粒体,细胞进行自杀的能力受到损害。一些癌细胞变得生物上不老不死。
DCA激活PDH酶,因此线粒体得以恢复,它们的膜极化得以正常化,细胞凋亡机制得以恢复。在健康细胞中,使用DCA治疗时没有检测到变化。
DCA功能的实验技术包括监测线粒体膜的极化。癌细胞培养物被染色并在共聚焦显微镜下观察。在大约5-10分钟的NaDCA应用后,线粒体的极化恢复正常,癌细胞经历凋亡,而正常细胞则没有任何变化。
关于实验问题的补充信息存储在此处。如果您有访问共聚焦显微镜的权限并希望为这项研究做出贡献,请与我们联系。
更新于2010年12月1日:
目前,我们已经开始一项实验,测试肉瘤细胞是否对DCA治疗产生脆弱性。
Zbigniew Karkuszewski,2009 年 1 月 5 日
Two years have passed since the seminal workof Canadian researchers on a drug that destroys cancer cells while leaving healthy tissue undamaged.
The substance is called DCA (dichloroacetic acid) and is used in the form of sodium salt NaDCA dissolved in water.
The drug is today in second stage of clinical trials (human patients) conducted in University of Alberta, Canada. The official DCA website is located here.
Oprócz oczywistej szansy ratowania ludzkiego życia badanie te oferują interesujące wyjaśnienie sposobu działania raka. Uczeni sugerują, że większość raków nie jest chorobą o podłożu genetycznym ale raczej metabolicznym. I to taką, na którą lekarstwo wymyślono i używano już dawno, ze znanymi skutkami ubocznymi.
Aby docenić prostotę pomysłu należy poznać kilka szczegółów oddychania komórkowego.
Każda żywa komórka w naszych ciałach potrzebuje energii do podtrzymywania czynności życiowych. Energia ta pochodzi ze strawionego pożywienia, które do komórek dociera w postaci cząsteczek glukozy. W procesie oddychania komórkowego energia zmagazynowana w wiązaniach chemicznych glukozy jest przenoszona do cząsteczek ATP (adenozyno-tri-fostoran).
Besides its considerable potential as a life saver DCA has also a scientific appeal because it offers a single explanation of inner workings of many distinct cancers. Namely, it suggests that cancer is a metabolic disease rather than genetic.
To appreciate that point let position it in the large picture of cellular respiration.
Each living cell in our bodies needs to produce energy in a form suitable to fuel necessary biochemical reactions. The process of energy conversion is called a cellular respiration and the goal is to store energy in ATP molecules.
The original energy comes from digested food that reaches cells in the form of glucose molecules and here the respiration starts.
The respiration in many cancer cells stops on glycolysis because their mitochondria are disabled due to the inhibition of mitochondrial gate-keeping enzyme pyruvate dehydrogenase (PDH). Glycolysis is less efficient in energy production than mitochondria-based glucose oxidation and a cell must use up more glucose to sustain its live. This higher glucose uptake is actually exploited in positron emission tomography with fluorodeoxyglucose (FDG-PET) that is routinely used for cancer detection.
Disabled mitochondria have hyperpolarized inner membrane and this electrostatic potential build up keeps cell’s apoptotic agents confined to mitochondria and cell ability to commit suicide is impaired. Some cancer cells become biologically immortal.
The DCA activates the PDH enzyme, thus mitochondria are revived, their membrane polarization normalizes and cell apoptotic mechanisms are restored.
In healty cells, no changes are detected under DCA treatment.
The experimental technique of the DCA function consists on monitoring the mitochondrial membrane polarization. Cultures of cancer cells are stained and observed under a confocal microscope. After about 5-10 min of NaDCA application the mitochondrial polarization returns to normal and cancer cells undergo apoptosis while nothing happens to normal cells.
The supplemental information on the experimental issues is stored here. If you have an access to a confocal microscope and would like to contribute to this research, please, contact us
Update December 1, 2010:
Currently, we have started an experiment that will test if sarcoma cells are vulnerable to the DCA treatment.
Zbigniew Karkuszewski, January 5-th 2009