迈亚密大学:辅酶Q10:一种温和的癌细胞杀手
CoQ10 a gentle cancer killer
2003年7月22日,Miller 医学院的NIVEN R.NARAIN 和他的研究生团队做了一个简单的实验。
利用手头上的材料,他们用辅酶Q10-一种抗氧化剂,治疗体外培养的黑色素瘤细胞。当他们第二天返回实验室时,他们有一个惊奇的发现:几乎所有的培养基里的癌细胞都死掉了。他们完全不知道发生了什么情况。NIRAIN回忆道。此外,他们开发了一种局部使用的辅酶Q10.
因为结果是如此惊人,研究人员认为他们的配方可能出了问题,他们仔细地重复实验。他们收到了同样的结果。在实验室和动物研究中,UM研究人员发现,通过向癌细胞和组织提供CoQ10,分子诱导细胞凋亡,这是在疾病过程中出错的正常程序性细胞死亡。
这已经不是Narain和其他研究人员第一次注意到CoQ10的应用可以杀死癌细胞,但是很难想象CoQ10,一种身体上的良性和自然的力量,会对任何东西造成伤害。该研究的主要研究人员、透皮传递/皮肤生物实验室主任、该研究的主要研究人员s.l. Hsia博士,多年来一直研究辅酶10(泛素酮),并创建了使该物质能够穿透细胞的磷脂基。“我们会去找Hsia博士说,‘你知道,这些细胞正在死亡’,他会说,‘那是什么机制?’”它怎么能杀死癌症呢?“Narain说。
CoQ10是人体中发现的最重要的抗氧化剂之一,它不仅可以用来抵抗自由基的破坏,还能产生ATP,这是一种能对人体细胞产生能量的化合物。高水平的CoQ10在高活性细胞中尤其重要,如心肌细胞、脑细胞和免疫系统细胞。随着年龄的增长,CoQ10的水平下降,而在癌症、糖尿病和神经退行性疾病中,抗氧化剂的水平也降低了。
CoQ10是由威斯康星大学的研究员Fred Crane发现的。在1957年,但直到最近二十年,抗氧化剂才开始用于治疗疾病。自1987年以来,研究人员一直关注CoQ10在肌肉疲劳、关节疼痛、心肌病和帕金森氏病中的应用。但是,米勒医学院皮肤科医学院的研究小组第一次“阐明了一种与癌症相关的特定细胞机制,”Narain说。
“鉴于CoQ10在线粒体中分布,线粒体在细胞中起着至关重要的作用,我认为随着时间的推移,人们会对CoQ10进行更多的调查,我们将会看到它的生理学的新角色。”就像一个大洋葱。当我们继续分解洋葱时,我们发现在一层,有一种抗氧化作用。我们继续解体,然后我们找到了对抗癌症的武器。随着我们不断前进,我们可能会发现越来越多的用途。
关于CoQ10的研究,最引人注目的发现之一是,这种疗法看起来是多么的温和和无害:“在服用CoQ10时,没有明显的副作用,”Narain说。
“令人惊奇的是,一种良性的化合物,CoQ10,能使癌细胞有选择性地杀死自己而不损害正常细胞,”Hsia说。“此外,我们还有一个新颖的药物传递系统,它为癌症患者提供了一种提高生活质量的能量。”事实上,我们的团队期待有一天能给许多癌症患者带来这项技术带来的好处和希望。
科学家们在今年春天的两次会议上展示了他们的发现。第一个陈述涉及到最常见的前列腺癌细胞系PC3。研究人员发现,通过在体外或实验室中加入CoQ10,在48小时内,细胞生长抑制率达到70%,而关键抗凋亡蛋白bcl-2的表达逆转。在第二份报告中,研究人员展示了CoQ10对几种不同乳腺癌细胞系的影响。他们发现这种物质能够极大地抑制乳腺癌细胞的增殖,同时对正常的乳腺细胞起到稳定的作用。“这提示我们,CoQ10在乳腺癌中可能是一种有效的辅助抗肿瘤药物,”皮科医生,皮肤科和皮肤外科的药物传递疗法的首席生物工程师说。
科学家们采用了多种方法来传递CoQ10,包括通过皮肤。他们用磷脂制成的脂质体作为分子载体,将皮肤病活性药物输送到靶向细胞中。“这项重要的工作是基础科学研究的重要成果的优秀模型,为探索生病病人的治疗方案提供了新的机会。这是我们所有人都在追求的实验室对床边的范例。他是皮肤科的系主任。
CoQ10的许多好处仍未被掩盖——包括一项与UM足球队测试CoQ10用于肌肉疲劳和关节疼痛的临床试验。“我不认为这是万能的,最终的分子,”纳拉因说。“但这确实是个好主意。”
https://s.click.taobao.com/uIoaKNw
COQ10 A Gentle Cancer Killer
http://www6.miami.edu/ummedicine-magazine/fall2005/fstory4.html
Because the results were so striking, the researchers thought perhaps something was wrong with their protocol, which they repeated carefully over and over again. They received the same results. In laboratory and animal studies, the UM researchers found that by delivering CoQ10 to cancer cells and tissues, the molecule induced apoptosis, which is the normal programmed cell death that goes awry in the disease process.
This was not the first time that Narain and the other research associates had noticed that this application of CoQ10 could kill cancer cells, but it was hard to imagine that CoQ10, a benign and natural force in the body, would be harming anything. S. L. Hsia, Ph.D., director of the Transdermal Delivery/Cutaneous Biology Laboratory and principal investigator of the research, had been working with ubiquinone for years and created the phospholipid base that enabled the substance to penetrate the cells. “We’d go to Dr. Hsia and say, ‘You know, these cells are dying,’ and he’d say, ‘What is the mechanism then? How can it kill cancer?’” says Narain.
CoQ10 is one of the most important antioxidants found in the body and is used by cells not only to protect against free radical damage but also to produce ATP, a compound that powers every cell in the human body. High levels of CoQ10 are especially essential in the high-activity cells, such as heart muscle cells, brain cells, and immune system cells. As we age, CoQ10 levels drop off, and decreased levels of the antioxidant have been observed in cancer, diabetes, and neurodegenerative diseases.
CoQ10 was discovered by University of Wisconsin researcher Fred Crane, M.D., in 1957, but it’s only in the last two decades that the antioxidant began to be used in the treatment of disease. Since 1987, researchers have been focusing on the application of CoQ10 for muscular fatigue, joint pain, cardiomyopathy, and Parkinson’s disease. But the research team in the Miller School of Medicine’s Department of Dermatology is the first to “elucidate a specific cellular mechanism for CoQ10 that’s involved in cancer,” says Narain.
“Given that CoQ10 is resident in the mitochondria, and the mitochondria plays a very crucial role in the cell, I think as time goes on and people do more investigation into CoQ10, we are going to see new and novel roles for its physiology. It’s like a huge onion. And as we continue to unravel that onion, we find in one layer, there’s an antioxidant effect. We continue to unravel, and then we find a weapon against cancer. As we keep going, we may find more and more uses,” says Narain.
One of the most striking findings about the CoQ10 studies is how gentle and nontoxic the therapy appears to be: “There is no evident side effect per se to taking CoQ10,” Narain says.
“It is amazing that a benign compound, CoQ10, can cause the cancer cells to selectively kill themselves without harm to normal cells,” Hsia says. “Moreover, we have a novel topical delivery system that offers cancer patients an improved quality of life with a boost of energy. Indeed, our team looks forward to one day bringing the benefit and hope of this technology to many cancer patients.”
The scientists presented their findings at two meetings this spring. The first presentation involved the most common prostate cancer cell line, PC3. The researchers showed that by adding CoQ10 to the cells in vitro or in the laboratory, there was a 70 percent inhibition of cell growth over 48 hours and a reversal in the expression of a key anti-apoptotic protein, bcl-2. In the second presentation, the researchers showed the impact of CoQ10 on several different breast cancer cell lines. They found the substance greatly inhibited the proliferation of breast cancer cells while providing a stabilizing effect on the normal mammary cells. “This suggests to us that CoQ10 could be an effective adjuvant anti-tumor agent in breast carcinomas,” says Indushekhar Persaud, chief bioengineer for drug delivery therapeutics in the Department of Dermatology and Cutaneous Surgery.
The scientists have employed various ways to deliver the CoQ10, including through the skin. They used liposomes made of phospholipids as a molecular vehicle to deliver dermatologically active agents into targeted cells. “This significant work is an excellent model for the important outcomes of basic science research to offer new opportunities for exploring therapeutic options in ill patients. It is the laboratory bench-to-bedside paradigm we all seek,” says Lawrence Schachner, M.D., chairman of the Department of Dermatology.
The many benefits of CoQ10 are still being uncovered—including a clinical trial with the UM football team testing CoQ10 for muscle fatigue and joint pain. “I don’t think this is the cure-all, end-all molecule,” says Narain. “But it’s certainly a good one.”