https://www.fightaging.org/archives/201 ... stasis.php
The process of metastasis is why malign cancers of all sorts turn out to be fatal in the end: their cells spread throughout the body to establish new tumors and outpace the ability of present treatments to keep up. The promise of the near future of cancer medicine is largely predicated on its ability to deal with metastasis. One approach is the use of targeted cell killing technologies that recognize cancer cells by their surface chemistry, capable of chasing down errant cells wherever they are in the process of spreading or building tumors. I think this is likely the type of treatment that will dominate the next generation of cancer treatments, as a range of different approaches to targeting are presently well advanced in the laboratory and clinical trials: immune therapies, simple nanomachines, engineered viruses, and so forth.
Another approach is to interfere with the process of metastasis in order to shut it down or at least suppress it, which would make many types of cancer more amenable to successful treatment with present day standards of surgery, radiotherapy, and chemotherapy. There hasn't been a great deal of success in suppressing metastasis in comparison to development of means to target cancer cells, but nonetheless a few approaches have been attempted. In the paper quoted below, researchers suggest that use of mitochondrially targeted antioxidants might be effective as a means of reducing metastasis to very low levels. If this bears out, it may attract more interest in the development of these compounds, which have been demonstrated to modestly extend life in mice as well as showing promise as treatments for a range of conditions.
Mitochondrial DNA damage is implicated in the progression of aging, and one theory is that this damage is caused by the generation of reactive oxygen species (ROS) within the mitochondria in the course of ordinary operation. So in theory life-long treatment with mitochondrially targeted antioxidants, carefully engineered compounds quite different from the antioxidants you can buy in a supplement store, will extend life by soaking up some of those ROS before they cause harm. As an approach to extending life this is poor in comparison to methods of mitochondrial damage repair, however. It can only slow the progression of aging somewhat, not turn back the clock.
Researchers at UCL identify a treatment that prevents tumor metastasis
Quote:
[Researchers have] succeeded in pinpointing a family of pharmaceutical compounds whose action prevents the appearance of tumor metastasis. The researchers achieved this tour de force by studying the mitochondria in tumor cells. These organelles are considered as the cells' power station. But when their functioning is altered, as [the] researchers observed in tumor cells, the mitochondria can promote cell migration, thus leading to the formation of metastasis.
[The researchers] examined the molecular mechanism responsible for the mitochondria's ability to promote metastasis. They succeeded in showing that, under certain conditions, the mitochondria produce more free radicals known as superoxide ions (O2.-). It is this overproduction of superoxide that leads to the formation of metastasis and, consequently, the growth of a tumor. Involved in other human pathologies such as Parkinson's and Alzheimer's disease, the production of superoxide by the mitochondria can be blocked by very specific antioxidants such as MitoTEMPO. Used in models of murine and human tumors, these compounds turned out to be very efficient at blocking the migration of tumor cells and preventing the spontaneous formation of human tumor metastasis in mice.
A Mitochondrial Switch Promotes Tumor Metastasis
Quote:
Metastatic progression of cancer is associated with poor outcome, and here we examine metabolic changes underlying this process. Although aerobic glycolysis is known to promote metastasis, we have now identified a different switch primarily affecting mitochondria. The switch involves overload of the electron transport chain (ETC) with preserved mitochondrial functions but increased mitochondrial superoxide production. It provides a metastatic advantage phenocopied by partial ETC inhibition, another situation associated with enhanced superoxide production. Both cases involved protein tyrosine kinases Src and Pyk2 as downstream effectors. Thus, two different events, ETC overload and partial ETC inhibition, promote superoxide-dependent tumor cell migration, invasion, clonogenicity, and metastasis. Consequently, specific scavenging of mitochondrial superoxide with mitoTEMPO blocked tumor cell migration and prevented spontaneous tumor metastasis in murine and human tumor models.
(Bolding added by me)Age-related arterial endothelial dysfunction, a key antecedent of the development of cardiovascular disease (CVD), is largely caused by a reduction in nitric oxide (NO) bioavailability as a consequence of oxidative stress. Mitochondria are a major source and target of vascular oxidative stress when dysregulated. Mitochondrial dysregulation is associated with primary ageing, but its role in age-related endothelial dysfunction is unknown. Our aim was to determine the efficacy of a mitochondria-targeted antioxidant, MitoQ, in ameliorating vascular endothelial dysfunction in old mice. Ex vivo carotid artery endothelium-dependent dilation (EDD) to increasing doses of acetylcholine was impaired by ∼30% in old (∼27 months) compared with young (∼8 months) mice as a result of reduced NO bioavailability (P < 0.05). Acute (ex vivo) and chronic (4 weeks in drinking water) administration of MitoQ completely restored EDD in older mice by improving NO bioavailability. There were no effects of age or MitoQ on endothelium-independent dilation to sodium nitroprusside. The improvements in endothelial function with MitoQ supplementation were associated with the normalization of age-related increases in total and mitochondria-derived arterial superoxide production and oxidative stress (nitrotyrosine abundance), as well as with increases in markers of vascular mitochondrial health, including antioxidant status. MitoQ also reversed the age-related increase in endothelial susceptibility to acute mitochondrial damage (rotenone-induced impairment in EDD). Our results suggest that mitochondria-derived oxidative stress is an important mechanism underlying the development of endothelial dysfunction in primary ageing. Mitochondria-targeted antioxidants such as MitoQ represent a promising novel strategy for the preservation of vascular endothelial function with advancing age and the prevention of age-related CVD.
http://www.ncbi.nlm.nih.gov/pubmed/24665093
