高压氧增强青蒿素的抗癌效力

Oxygen enhances artemisinin’s cancer killing capacity

　

　

　

　

2011年4月5日

 

据报道，迈克尔·杰克逊为了延长自己的青春而使用的一种治疗癌症的方法被证明是有效的。

 

华盛顿大学(University of Washington)和华盛顿州立大学(Washington State University)的研究人员最近在《抗癌研究》(Anticancer Research)杂志上发表报告称，在3.5倍正常气压的纯氧环境下，一种已经被证明可以杀死癌细胞的天然化合物的效力显著增强。

 

从青蒿中分离出的复方青蒿素，通常被称为青蒿，是一种广泛用于治疗疟疾的天然药物。20世纪90年代中期，华盛顿大学的研究人员首次探索了它治疗癌症的能力。

 

在新的研究中，使用青蒿素或高压氧单独在人类白血病细胞培养中降低了15%的癌细胞生长。联合使用它们可以使细胞生长减少38%，使青蒿素的有效性增加50%。

 

“我们只测量了48小时，”作者亨利·赖(Henry Lai)说，他是华盛顿大学生物工程学研究教授。“长期来看，我们预计协同效应将更为显著。”

　

　

 

在一个古老的棺材里(长沙马王堆）的药方

青蒿素的历史让人想起了印第安纳·琼斯的故事。赖教授说，上世纪70年代初，中国领导人毛泽东下令发展一种抗疟疾疗法。与此同时，中国中部的一位农民发现了一座有2000年历史的坟墓，里面有三具棺材。

 

其中一副棺材里有一幅丝绸卷轴，上面写着各种各样的处方，包括治疗疟疾的青蒿素。中国人按照指示重新发现了一种古老的疗法。

 

今天，青蒿素在亚洲和非洲广泛用于疟疾治疗。

 

在此后的几十年里，科学家们发现青蒿素与细胞内的铁发生反应，形成自由基，这是一种能破坏细胞的高活性带电粒子。因为疟疾寄生虫富含铁，青蒿素的目标是感染疟疾的细胞。

 

由于快速分裂的癌细胞也需要铁来形成新的DNA, Lai推测癌细胞也会成为青蒿素的标靶。后来的研究表明这是事实。

　

　

 

青春之泉

赖和他在UW的同事开发了一种比天然青蒿素强几千倍的变种，这种青蒿素在2004年被授权给一家中国公司。

 

“青蒿素是一种很有前途的低成本癌症治疗方法，因为它有高度的选择性、便宜的，你不需要注射它，”赖说。他补充说:“这比传统的化疗要精确100倍。”“对于乳腺癌来说，甚至更好。”

 

赖说，他长期以来一直假设高氧水平会增强青蒿素的作用，因为氧促进自由基的形成。2010年，他在一间高压氧舱里对这一理论进行了测试。该实验室的合著者、威斯康辛大学(WSU)教授、制药科学主席雷蒙德•科克(Raymond Quock)一直在利用该理论研究高压氧缓解疼痛的能力。

 

高压氧舱，在高压下充满氧气，帮助潜水者迅速浮出水面，逐渐调整到正常的氧气水平。80年代中期，流行歌手杰克逊躺在便携式高压氧舱里的一张照片引发了人们的猜测:他试图治愈整形手术留下的疤痕，保持年轻的外表，或者延长寿命。

 

这张照片被证明是一个宣传噱头，但是美国食品和药物管理局已经批准了一些疾病的高压氧疗法，包括减压病、一氧化碳中毒、严重烧伤和缓慢愈合的伤口。

 

潜在的经济作物

在临床实践中，青蒿素高压氧的研究可能会导致人或动物在高压氧室内呆上一段时间，以提高青蒿素的有效性。

 

其他合著者还有尤素科·大加米、凯瑟琳·埃尔斯塔德、威斯康辛大学的郑云熙和芝加哥高压氧中心的唐纳德·Shirachi。这项研究由WSU药学院和芝加哥高压氧中心资助。

 

在相关的青蒿素研究中，由国家生命科学发现基金提供的150万美元资金资助给一个由UW化学教授佐佐木知和领导的团队:

 

�华盛顿大学的研究人员正在开发合成青蒿素、具有增强的力量和抗癌选择性,和华盛顿州立大学的研究人员正在进行一个临床试验评估这些化合物治疗癌症的能力在狗。这些分子设计的青蒿素化合物比天然青蒿素更强、更有针对性，但仍可口服，被授权给纽卡的艾特米西生物医药公司(Artemisia Biomedical)。

 

Oxygen enhances artemisinin’s cancer killing capacity

April 5, 2011

PULLMAN, Wash. – A technique Michael Jackson reportedly used to prolong his youth is showing promise as a way to boost the effectiveness of a natural cancer remedy.

 

An environment of pure oxygen at 3.5 times normal air pressure adds significantly to the effectiveness of a natural compound already shown to kill cancerous cells, researchers at the University of Washington and Washington State University recently reported in the journal Anticancer Research.

 

The compound artemisinin – isolated from Artemisia annua L, commonly known as wormwood – is a natural remedy widely used to treat malaria. In the mid-1990s UW researchers were the first to explore its ability to treat cancer.

In the new study, using artemisinin or high-pressure oxygen alone on a culture of human leukemia cells reduced the cancer cells’ growth by 15 percent. Using them in combination reduced the cells’ growth by 38 percent, a 50 percent increase in artemisinin’s effectiveness.

“We only measured up to 48 hours,” said author Henry Lai, a UW research professor of bioengineering. “Over longer time periods we expect the synergistic effects to be even more dramatic.”

Prescription in an ancient coffin

 

The history of artemisinin brings to mind an Indiana Jones story. In the early 1970s, Lai said, Chinese leader Mao Zedong issued an order to develop an anti-malarial treatment. At the same time, a farmer in central China discovered a 2,000-year-old tomb that contained three coffins.

 

One coffin contained a silk scroll describing various prescriptions, including artemisinin to treat malaria. The Chinese followed the directions and thus rediscovered an ancient remedy.

Today, artemisinin is widely used in Asia and Africa for malaria treatment.

In the decades since, scientists have discovered artemisinin reacts with iron within a cell to form a free radical, a highly reactive charged particle that destroys the cell. Because the malaria parasite is high in iron, artemisinin targets malaria-infected cells.

Since rapidly dividing cancer cells also need iron to form new DNA, Lai theorized they would also make targets for artemisinin. Subsequent research showed this to be the case.

Fountain of youth

Lai and colleagues at the UW developed a variant several thousand times more potent than natural artemisinin, which was licensed in 2004 to a Chinese company.

“Artemisinin is a promising low-cost cancer treatment because it’s specific, it’s cheap and you don’t have to inject it,” Lai said. “It’s 100 times more specific than traditional chemotherapy,” he added. “In breast cancer, it’s even better.”

 

Lai said he has long hypothesized that high oxygen levels would enhance artemisinin’s effects, because oxygen promotes the formation of free radicals. In 2010, he put the theory to the test in a hyperbaric chamber that co-author Raymond Quock, WSU professor and chair of pharmaceutical sciences, has been using to study highly pressurized oxygen’s ability to relieve pain.

Hyperbaric chambers, filled with oxygen at high pressure, help scuba divers who surface too quickly gradually readjust to normal oxygen levels. A photo of pop singer Jackson in the mid-80s sleeping in a portable hyperbaric chamber sparked rumors that he was trying to heal scars from plastic surgery, retain his youthful appearance or extend his lifespan.

 

The photo turned out to be a publicity stunt, but the U.S. Food and Drug Administration has approved hyperbaric oxygen therapy for several ailments, including decompression sickness, carbon-monoxide poisoning, severe burns and slow-to-heal wounds.

 

Potential for commercial crop

In clinical practice, the artemisinin-hyperbaric study could lead to people or animals spending time in a hyperbaric chamber to enhance the artemisinin’s effectiveness.

Other co-authors are Yusuke Ohgami, Catherine Elstad and Eunhee Chung of WSU and Donald Shirachi of the Chico Hyperbaric Center. The research was funded by the WSU College of Pharmacy and the Chico Hyperbaric Center.

 

In related artemisinin work, funded through a $1.5 million grant from the state’s Life Sciences Discovery Fund to a team led by UW chemistry professor Tomikazu Sasaki:

� UW researchers are developing synthetic artemisinin compounds with enhanced potency and anti-cancer selectivity, and WSU researchers are conducting a clinical trial evaluating these compounds’ ability to treat cancer in dogs. The molecular-engineered artemisinin compounds, which are stronger and more targeted than natural artemisinin but can still be taken by mouth, are licensed to Artemisia Biomedical of Newcastle, Wash.

� WSU crop scientists are planting Artemisia annua in eastern Washington to test whether the region could plant artemisinin as a commercial crop.

� Researchers are working with Northwest Organic Foods, a Washington chicken-feed company, to try adding artemisinin, instead of small amounts of arsenic, to chicken feed. Artemisinin acts as a natural preventive for avian coccidia infection, one of the poultry industry’s most costly parasitic diseases.

 

Oxygen enhances natural cancer treatment | WSU Insider | Washington State University  https://news.wsu.edu/2011/04/05/oxygen-enhances-natural-cancer-treatment/