N-Acetyl-Cysteine

Recommendation:  DO NOT TAKE (without medical supervision)*       INCLUDES section on Cyr61 and Cancer

NOTE: NAC is often recommended for diabetes control since it increases the antioxidant Glutathione Peroxidase. This article is about the relationship of NAC to cancer and not as diabetes control aid. But both conditions need to be a factor for consideration when NAC is supplemented. NAC is a ROS or oxidative stress reducer. Since ROS is involved in skin breakdown, NAC plays a beneficial support.

If one searches the internet for NAC effects on cancer, overwhelming positive studies surface first and lead to an apparent verification of NAC use to stop or slow down many cancers. BUT, there are also some potential adverse effects for some cancers that call for caution with NAC. When and how to approprietely use NAC is the question?

*A very complex nutrient. Because cancers can take such a long time to manifest, taking NAC for one of it's many benefits could jeopardize health if certain types of cancers are already developing. Work with your health care professionals for health check ups to spot cancers early. See * below. ref  This reference appears to miss some vital cancer problems with NAC on the CYR61 pathway. This is a secondary process since NAc provides the body with cysteine, a part of NAC.    

This is perhaps the best example of a nutrient with many benefits (such as an expectorant plus as a chemopreventive agent) but also with a few potential negatives not mentioned often enough. ref  Here are some of the positive actions.  ref  ref ref  ref  ref  The cancer applications mentioned are significant since NAC influences Glutathione, GSH, production in cells.  ref  ref  and in anti-cancer drug interference, not a desirable happening. >ref ref

Attempting to find out how NAC and thus GSH influence cancer, it was found that among the many positive cancer inhibiting functions for NAC, a twist was also found that NAC increased production of Cyr61, which has shown both tumor promoting and surpassing aspects in different cancers. First, the following study shows NAC reduces prostate cancer cell growth by mechanisms that eventually lead to the over expression or production of Cyr61, also known as CCN1.  ref  ref  This reference shows higher Cyr61 protective against Prostate Cancer spreading, while the next is a study showing how higher Cyr61 levels correlate with more aggressive non organ contained prostate cancers. There is a piece missing in this puzzle. Thus the precautionary approach to limit supplementation is necessary until these issues are researched in more detail.

It has often been found that a nutrient under study will decrease the slower growing form of prostate cancer while increasing the less seen aggressive form, or vice versa.  ref  In this study, higher Cyr61 means lower risk of Prostate cancer coming back after treatment.  The action of Cyr61 in some cases might protect against Prostate cancer spreading by triggering a unique counter response in another pathway. ref  While other studies show a higher level associated with greater spreading and aggressiveness of cancer? Here is how it works and might do both. ref  There is a balancing effect of CCN3 on CCN1, or Cyr61. This is an intense area of cancer research right now. Sooner rather than later the results should become clearer. Between CCN-1 and CCN-2 ref

To continue to show greater complexity for this element, here is copy from a breast cancer study on Cyr61:

"We have shown that Cyr61 is overexpressed in invasive and metastatic human breast cancer cells and tumor biopsies (Tsai et al.," 2000). In addition, we demonstrated that Cyr61 function is necessary for heregulin (HRG)-mediated chemomigration of breast cancer cells (Tsai et al., 2000). We further determined that Cyr61 is sufficient to promote breast cancer cells to bypass their normal estrogen requirement for growth, to induce progression of breast cancer cells to more aggressive and invasive phentoypes in vitro, and to induce tumor formation in vivo (Tsai et al., 2001, manuscript submitted)."  ref    ref

Plus another study showing how low oxygen levels in body cells lead to Cyr61 expression. study

Skin Health and CCN1 (Cyr61)

Here is another twist to this story. CCN1 levels are elevated at sites of skin collagen breakdown. ref  article

WHAT DOES THIS MEAN

NOTE: First, not mentioned is that GSH production increased by NAC concerns Doctors because GSH protects cells against the action of chemo drugs. Cancer Doctors give patients one drug to first decrease GSH production so that the chemo drug can function and kill cancer cells. But this leaves the normal cells open to ROS (reactive oxygen species, or oxygen radicals) damage, presenting a dilemma for Oncologists. NAC was thought to be beneficial against cancer initiation due to it's ability to increase GSH and act like an anti-oxidant to protect cells against ROS damage. It may be working too well as the cancer drugs are looked at like a radical and destroyed when GSH is elevated.

Now, is Cyr61 a good element or a bad element concerning cancer growth?

In the men's study above positive effects of NAC found for cancer also generated increased Cyr61 levels. In this case, the increased Cyr61 generated a controlled release of ROS radicals that proved beneficial to the function of other elements created in this cascade of effects started by ROS. Cyr61 may have positive influence at some prostate cancer stages while negative ones at other stages, especially later more advanced ones. Also the expression level may vary depending on the activity of other elements which determine how Cyr61 functions in cell adhesion, proliferation, and cell death mechanisms. These functions are critical in cancer cells since they do not die like normal cells (apoptosis) and love to spread throughout the body. Cyr61 becomes a target for cancer researchers just because this is how it naturally functions. Measuring levels of Cyr61 may give Doctors a good indication about how cancers will progress. Some organ-contained prostate cancers are very slow growing and don't need aggressive treatments. 

In the breast cancer study, greater Cyr61 was associated with detrimental outcomes. Or, maybe it is under the influence of estrogen. Do cancer cells first develop and then over-express Cyr61? Or does the over-expression lead to cells becoming cancerous? Cry61 is not always over-expressed in all cancers. Thus, it must take other related factors to direct it's response. The most likely happening is that Cyr61 expression gets dysregulated, does not function correctly in nature's controlled plan, and gets either over or under-expressed. Is the cancer cell smart enough as it is with other nutrients to actually cause the over-expression of Cyr61 so cancer cells can grow faster? Like using vitamin B1 for faster growth or eliminating interfering vitamin D activation and speeding it's breakdown to less effective cancer fighting forms.

BACK TO NAC INFLUENCE

And now lastly, does supplemental NAC increase the production of Cyr61 as the prostate study reported? Cyr61 stands for cysteine-rich protein 61. NAC contains cysteine. NAC can act as either a pro-oxidant or an anti-oxidant. ref 

Scientists can modify conditions to determine which oxidative function NAC will perform. This gives greater power to control cancer behavior. Watch for more cancer treatments based upon this knowledge soon. ref  Cyr61 expression is a major player in both health and disease.

Yes, Cyr61 appears to have both benefits and detriments. It is needed in just the right amounts to properly heal wounds without excessive scarring. Funny thing, this benefit is derived from it's ability to create damage in cells, the ROS pathway, setting off a cascade of events that eventually leads to the desired positive healing process. Nature's grand design. ref

This report best sums up the CCN family actions of which Cyr61, or CCN1, may be the most important.

*RECOMMENDATION: DO NOT TAKE N-ACETYL-CYSTEINE unless directed by a medical practitioner until it's influence on Cyr61 levels, direction of Cyr61 effects, and your body conditions are known. You often do not know if you already have a growing cancer before it is too late. It might be OK to use NAC for short periods at moderate dosages in certain conditions described here. Sometimes drastically different actions occur as dosages vary and go past regular dietary amounts. It appears wise to also take vitamin C to prevent cysteine for turning into kidney stone forming format. Here is a report on exercise and NAC functions. Still more to learn.

OF INTEREST: Vitamin D has a transient stimulatory effect on Cyr61 expression??? ref Is this a positive or a negative for vitamin D???  Could be either depending upon disease stages and body conditions. Did you notice that vitamin A has the opposite effect? Maybe they balance each other.

Summary copied from abstract referenced above:

"In summary, we have demonstrated that Cyr61 is regulated by E2 (Estrogen), and that anti-estrogens can block this induction in MCF-7 cells (most common of 4 types of breast cancer, Estrogen Receptor-positive). Interestingly, we determined that a possible negative regulator of Cyr61 is present in MCF-7 cells. By contrast, the effects are different when Cyr61 overexpressing cells are treated with these agents. In addition, we demonstrated that both TPA and vitamin D up-regulate the expression of Cyr61 in breast cancer cells that express high levels of ER, such as MCF-7 cells. In contrast, the differentiating agent RA inhibits the expression of Cyr61 in MCF-7 cells. All of these results are consistent with our previous findings that Cyr61 promotes breast cancer cells and tumor growth, and that tumor-promoting agents have a positive impact on cells in which Cyr61 expression is low, whereas these agents have no significant effect on cells that express high levels of Cyr61. On the other hand, down regulation of the growth-promoting activity of Cyr61 by RA may account for the ability of RA to induce growth inhibition and apoptosis in breast cancer cells.

In conclusion, we demonstrate that regulation of Cyr61 is involved in breast cancer progression, and that Cyr61 should be considered as a new target for therapy. We have demonstrated that Cyr61 is highly expressed in breast carcinomas and that it induces the progression of breast cancer in vitro and in vivo. We are therefore currently investigating the mechanisms that account for Cyr61 induction of breast cancer progression."

 Analysis:

Recommendation:  DO NOT TAKE NAC without medical supervision. Yes, NAC has many beneficial functions on ROS elimination and resulting prevention of some cancers. BUT, along with many beneficial antioxidant actions, there are a few pro-oxidant ones that need to be monitored for certain subsets of the population. Does NAC increase GSH enough to interfere with the cancer destroying actions of certain chemo-drugs?