Reactive oxygen species (ROS) such as superoxide anion radical, singlet oxygen and hydrogen peroxide appear to be important for the promotion, initiation, progression and maintenance of cancer cells. ROS signaling plays important roles in normal biological functions, such as promoting cell proliferation. Increases in ROS production can also lead to increased genome instability through damage to DNA and DNA associated proteins such as chromatin. Cancer cells in some instances may down-regulate antioxidant enzymes (which are important in reducing ROS levels) for the purpose of increasing ROS levels for driving cellular proliferation. Other cancers may up-regulate antioxidant enzymes to help protect against damage from ROS. These adaptive responses are probably dependent upon ROS levels which probably vary between cancer cell types. Since increased levels of ROS in cancer cells is seen as a bad thing, many therapies (such as enhancing ROS scavenging enzymes) in development are focused on reducing ROS levels. This strategy is hoped to reduced genomic instability which could lead to more aggressive cancers and reduce proliferation in these cells. More recently, it appears the opposite approach is being taken. Since ROS levels are already high in cancer cells, increasing the levels further may tip the balance and trigger cells death instead. In normal cells, the response to ROS can vary depending on the levels. Lower levels of ROS may lead to DNA damage which triggers growth arrest so that the cell can repair the damage. Increasing ROS levels further may result in irreparable damage and so the cell may enter a state of senescence (permanent growth arrest). Increasing ROS levels even further can cause so much damage that the cell undergoes apoptosis or even necrosis. So a cancer cell that already has high levels of ROS may only need a little more to induce death. Importantly, it is hoped that the levels of ROS needed to increase death in cancer cells is insufficient to cause death (or senescence for that matter) in healthy cells, which may be important for drugs that are non-specific.
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Longevity research and ageing research are sometimes treated as one of the same, and this is not entirely true. Longevity research is predominantly focused on investigating factors (such as the over expression of certain genes) which extend life-span (longevity) of a model organism (often fruit flies, worms and mice). Ageing research is more concerned with biological mechanisms of ageing, such as oxidative stress or cellular senescence for example. Of course there is overlap between longevity research and ageing research. In longevity research, biological alterations (or intrinsic factors) which have led to life extension in an organism is probably the result of modulating a mechanism of ageing. The difficulty is knowing what the altered mechanism may be. Similarly, increased longevity of an organism is often used as a parameter to determine successful modulation of a particular mechanism of ageing.
Does ageing cause cancer? Or does cancer cause ageing? That is the question. Most people reading this may think the answer is obvious, that ageing leads to cancer. The general public’s mindset about ageing is normally associated with oxidative stress and the damage it can cause to proteins and DNA (mainly due to media coverage and beauty products). Increases in DNA damage (and mutations) with age are thought to be associated with the increase incidences of cancer later in life. In some respect this may partly be true (although convincing evidence of this in humans is currently lacking in my opinion), but it is not the full story.
The human body has evolved mechanisms for preventing the appearance of cancer cells. One such mechanism is known as cellular senescence, an irreversible growth arrest of the cell. When oncogenes become activated they undergo onocogene-induced senescence (OIS), thus acting as a barrier to prevent aberrant growth and cancer formation. In addition to the permanent growth arrest, senescent cells appear to have a secretory phenotype which may aid the removal of the senescent cell by the immune system. Probably triggered by findings from Scott Lowe’s group, who in 2007 published an article which provided evidence for immune response of senescent cells, Dominick Burton went on to suggest that the secretory phenotype of senescent cells may function in the removal of senescent cells by the immune system…..” One possibility is that senescent cells secrete cytokines to attract immune cells to its location (for its removal), secretes matrix degrading proteins to allow the immune cells access and secrete growth factors to stimulate surrounding cells to proliferate once the cell has been removed” (Burton, 2008).
Senescent cells are known to accumulate in tissues as we age and Dominick suggested this might be due to a functional impairment of an ageing immune system. The accumulation of senescent cells in tissues is a bad thing. If senescent cells persist in tissues, the secretory factors which may have been intended for immune clearance are now constantly being released into the local microenvironment. These factors (cytokines, growth factors and proteases) are thought to alter the biological properties of the tissue in which they reside, thus causing ageing. In this regard, cancer causes ageing indirectly due to defects in mechanisms intended to remove potentially cancerous cells. Additionally, the Campisi group suggested that the secretory phenotype of senescent cells might also stimulate the appearance cancerous cells. So cancer leads to ageing which leads to even more cancer.
So to conclude, immune clearance of senescent cells my be extremely important in both preventing cancer and preventing ageing.