The human body is an amazing entity. It is composed of trillions of cells, each specifically engineered in order to function within its own section of the body, ultimately allowing the whole to survive. Cells are constantly created, in an extraordinarily brilliant and precise action that is almost flawlessly carried out millions of times each day. The creation of new cells in the human body is an amazingly precise process but there are countless opportunities for it to fail. Sometimes during the millions of cell divisions this process goes awry resulting in a cellular mutation. Although it does not take one mutation to cause cancer, the first mutation is an initial step towards it.
Once enough mutations occur, cancerous cells emerge. Treating cancer is an extremely difficult process both attacking the cancer cells and limiting the damage to healthy cells during this process. Chemotherapy is a common treatment for destroying tumors, yet its repercussions on the non-cancerous cells in the body is tremendous. A chemotherapy patient endures horrific pain and suffering from both the cancer and the treatment. Not only does this take a physical toll on the patient, but also an impalpable mental toll as well. In order to advance in the treatment of cancer, man needs to find a mechanism that not only allows for the chemotherapy treatment to work, but also negates its negative effects. Although the solution to this problem seems impossible, there may be an answer closer than we think.
In a recent study conducted by Dr. Guie Dong discussed in the American Journal of Physiology the problems associated with chemotherapy could be a thought of the past. The study’s focus was two anticancer agents’ cytoprotective effects of suberoylanilide hydroxamic acid (SAHA) and Trichostatin A (TSA). These chemicals inhibit histone deacetylases. The study was conducted on rat kidney proximal tubular cells in order to observe the effects of both SAHA and TSA in protecting healthy cells against cisplatin nephrotoxicity. If the chemicals could protect against DNA damage and associated p53 activation resulting in suppression of tubular cell apoptosis (cell suicide) in rats, the implications of this for humans would be tremendous.
The results of the study revealed a true potential for these chemicals, or similar more advanced chemicals, to aid in chemotherapy. During cisplatin treatment massive apoptosis occurs. In the experiment, the group that was just given cisplatin treatment the RPTC cell apoptosis was 53%, but when treated with SAHA prior to the cisplatin treatment the cell apoptosis was reduced significantly to 21%. Similarly, when RPTC cells were treated with TSA the cisplatin was reduced by 17%. Both chemicals inhibit the negative apoptosis that the cisplatin treatment causes. This part of the experiment was conducted over a short period of time. For practical use the success of SAHA and TSA needs to be long-term the experimenters also observed its success over an extended period. Forty-eight hours after cisplatin treatment the morphology and amount of cell protein recovered was observed for each of the experimental and control groups. In the group of RPTC cells that were just issued the cisplatin treatment the long-term effect was staggering. Almost no cell protein was recovered and the cell population was quite low. In stark contrast, the groups treated with SAHA and TSA observed a considerable difference. A large amount of protein was recovered and there was significant cell survival.
Another aspect of the experiment was to test the effects of SAHA and TSA on the signaling pathway that leads to cisplatin-induced renal cell apoptosis and DNA damage and p53 activation. One intrinsic property of HDAC inhibitors is that they block the structural alterations of chromosomes, which is an effect of cisplatin. Thus, this could aid in the cytoprotective effects of SAHA and TAS by protecting cells from DNA damage. A major cause in the damage to a cell’s DNA is caused by p53 activation. Through the results of the experiment it was determined that SAHA has a moderate, yet significant, influence by suppressing the effects of p53 which protects the RPTC cells during cisplatin. SAHA does not deflate the damage to DNA that is caused by cisplatin, yet it does interfere with an activation molecule (Chk2) that causes p53 activation. Similarly, TSA pretreatment leads to the suppression of cisplatin-induced p53 acetlyation. However, TSA does not have lasting effects, which suggests that this has the potential to slow down p53 activation.
Although it is important to limit the negative effects of chemotherapy, the integrity of the treatment must not be compromised because of its importance in fighting cancer. Thus, the experimenters observed the implications of SAHA and TSA treatment in its anti-cancer efficacy. The results of the experiment reveal that not only do the chemical not obstruct the apoptosis in HCT116 colon cancer cells but they also increase it. The combination of cisplatin and SAHA increased the apoptosis in the colon cancer cells from 20% (only using cisplatin) to 73%. Thus, it is possible to infer that while SAHA interferes with p53 signaling in RPTC cells, it increases the signaling in HCT116 cells to increase apoptosis.
The implications of these findings are tremendous. Not only are healthy cells that are not the target of the chemotherapy better protected, but also the cancerous cells that are targeted are more efficiently killed. Because the cells that are not targeted are less likely to be harmed the health of the cancer patient is infinitely increased. The long-term effects of cisplatin is damage to major organs located near the site of the treatment, yet with the results of this experiment this could be a thing of the past.
The article was invariably difficult to understand, yet the most important messages were clear. The article emanates a feeling of hope because of the exciting implications that these findings in rats can have in humans. However, it is clear that there is much work to be done in order to make the ideas discovered in the experiment applicable to humans. An improved method of treating cancer is an urgent matter. Through the continued research related to this experiment it is possible that cancer treatment can not only improve but have almost no negative side effects.
Dong, Guie, Jia Luo, and Zheng Dong. "HDAC Inhibitors Block P53 Activation." American Journal of Physiology (2009): n. pag. Web. 8 Nov 2009.