Cancer is inherently a genetic disease. Mutations in the genes of normal cells are paramount in the process of carcinogenesis. Genes predisposing to cancer can be inherited. The genes within each cell instruct that cell as to its size, shape, and activity. The genes determine every major aspect of how a cell will present phenotypically, and the genes control the activity and functions of each cell. The genotype specifies the phenotype. Genetic factors are therefore paramount in both the development of cancer cells and also in determining what harmful activities the cancer cells will have within the body. The realization of the importance of genes in oncology has led scientists to begin experimenting with ways to influence cancer genes and cause “genetic healing” in cancer.
Genetic healing can occur by many mechanisms. The best known of these mechanisms include 1) the direct incorporation of new “anti-cancer” genes into cancer cells, a concept which includes Telomerase gene therapy; 2) re-differentiation, and 3) apoptosis. Re-differentiation refers to the propensity of cancer cells to revert back to a normal, or perhaps simply to a “less-cancerous” state. This concept is premised upon the widely accepted theory that cancer cells are derived from cells that were once normal. The theory states that as the normal cell is placed under metabolic stress, it genetically mutates multiple times. Factors such as radiation, chemical toxins, and others comprise the stressors that result in step-by-step mutations. As each gene mutation occurs, the cell phenotypically becomes more abnormal. It is believed that this process occurs commonly in modern humans. Why then, do not more cells become cancerous? The answer is thought to be the genetic checks and balances inherent within each cell.
Genetic checks and balances are the major safety mechanisms protecting us from developing cancer. Each of our cells is born with a natural endowment of genes and genetic pathways that are protective against carcinogenesis. Cell-cycle control genes monitor perturbations in the cell cycle and other genes scan for aberrations within the genetic code as the cell replicates itself via mitosis. These genes can stop an abnormal cell from replicating, and attempt to repair the genetic damage which we often call a mutation. The genes involved in re-differentiation and apoptosis are thought to be crucial in the monitoring and abatement of carcinogenesis. Interestingly, mutations in these protective genes are thought to be imperative if a mutating cell is to survive long enough to become a tumor. Re-differentiation genes may become active during the process of transformation of a normal cell into a malignant cell. They attempt to reverse the cell’s progress down the genetic path towards malignancy and away from carcinogenesis. If the re-differentiation genes are successful, they will cause the mutating cell to take the same mutation steps backward and thereby unravel the stepwise process of mutations that can lead to cancer.
Apoptosis genes also protect against mutagenesis. Apoptosis is the process by which our genes monitor if aberrations in the genetic code are occurring and then cause the cell to go through a process of self-destruction if the genetic damage cannot be repaired. This process tends to delete cells that are mutating towards carcinogenesis. Many modern scientists believe that apoptosis, re-differentiation, and cell cycle control genes are the most important inherent protective mechanisms against neoplasia.
This concept is the antithesis of another theory held widely by the public and by alternative medical practitioners. That theory holds that it is the immune system that primarily protects us from developing cancer. Many people assume that the immune system should know if a cell is dangerous to the body. However, there is little credible scientific evidence to suggest that the immune system has any way to detect cancer cells, or that the immune system is designed to attack cancer cells. The immune system is designed to protect the body from foreign invaders such as bacteria. Immunity senses whether each cell is a “self cell” or a foreign cell. Unfortunately, the markers of most cancer cells indicate to the immune system that they are “self cells” and the immune system, therefore, ignores it. The so-called “immune surveillance system” against cancer is unlikely to have a significant impact on limiting neoplastic growth and development. This, however, does not preclude the immune system from being coaxed into attacking cancer cells when medical treatments such as cancer vaccine therapy are administered, but it does argue against any natural inherent immune protection against carcinogenesis. The genetic protection mechanisms seem to have that role.
Fundamental to carcinogenesis is the destruction or impairment of the genes that encode the apoptotic and re-differentiation pathways. We would therefore expect that tumor cells would have these genes either eliminated, turned off, or turned down. Cells that turn off or turn down their re-differentiation and apoptosis genes may potentially be prodded into turning these protective gene pathways back on. The process of re-differentiation may result in a partial reversion towards normalcy, in which case the cell simply becomes less cancerous. An active intra-cellular apoptotic mechanism results in an increased tendency of the mutating cell to sense that it has mutated, and then to self-destruct via complex genetic and cytosolic interaction. 1 Although the exact mechanisms involved in the apoptotic pathways have not yet been fully elucidated, researchers are gradually revealing the intricacies involved in this life-saving process. One of the most important genes in this process is called p53. Apoptosis research has indicated that p53 induces the release of cytochrome c from the intermembrane space of mitochondria and that Bax in the cytosol of the cell also plays a role. 1
R-A Therapy is a concept of utilizing existing natural substances in an attempt to induce re-differentiation and apoptosis in cancer cells, or in cells undergoing malignant transformation. The concept of genetic healing and preventive mechanisms in oncology is in its infancy. Nonetheless, there is credible scientific evidence that many natural substances may induce protective genetic mechanisms such as re-differentiation and apoptosis.
N-acetylcysteine is a very promising candidate for a natural substance that may induce apoptosis. N-acetylcysteine is a prominent component of the R-A Therapy regimen. Many recent scientific studies attest to the propensity of N-acetylcysteine to induce apoptosis and play other health-protective roles in the body. In alternative medicine, N-acetylcysteine is best known as an immune enhancer and antioxidant. However, in natural cancer therapy, its most important role may well be to induce genetic healing mechanisms. R-A Therapy relies upon the propensities of natural substances such as N-acetylcysteine to attempt the induction of genetic healing processes. N-acetylcysteine (NAC), along with another agent used in R-A Therapy known as dimercaptopropanol, have been shown to induce apoptosis in several cancerous (transformed) cell lines and several transformed tissue cultures. 2 Interestingly, NAC and diemercaptopropanol did not induce the apoptotic “cell-suicide” program in normal cells. These two agents caused the death of the transformed cells through apoptosis but did not cause death in the normal non-malignant cells. The mechanisms of action described in this study included the elevated post-transcriptional expression of the p.53 gene via an increase of p.53 mRNA translation. The authors of the cited study postulate that “manipulating p53-dependant apoptosis with non-toxic antioxidants may have a direct clinical application.”
NAC has also been shown to affect the genes involved in cell-cycle control, one of the postulated genetic healing and genetic protective mechanisms against cancer. NAC was shown in a recent study to induce G(1) cell cycle prolongation and cyclin-dependent kinase inhibitors, causing the authors of the study to postulate that “taken together, these results suggest a potential novel molecular basis for chemoprevention by NAC.” 3 In another research paper, published in the International Journal of Biological Markers, the authors described NAC as “a cytoprotective drug that can prevent in vivo carcinogenesis.” 4 The same research paper showed evidence that NAC reduced the weight of the primary tumors studied (an indirect indication of cancer cell death), diminished the number of lung metastases, and reduced the formation of spontaneous metastases in mice. The researchers also found that NAC seems to have an anti-angiogenesis effect. They discovered that NAC strongly reduced the invasive activity of endothelial cells when subjected to angiogenic stimuli and that NAC blocks gelatinase activity. In vivo anti-angiogenesis activity was detected and reported by the authors following the oral administration of NAC. Perhaps the most interesting finding of this study to clinicians is the fact that NAC inhibited tumor latency, and that this effect was dose-dependent. The significance of this finding is that one of the important precepts of R-A Therapy is that high doses of natural substances should be administered in a way that best presents the highest possible dose directly to the cells. Intravenous administration of natural substances is therefore a very important part of the R-A Therapy concept.
NAC is postulated to have effects on the genes of cancer cells and also serves as an antioxidant. More research is needed. More research is needed. These two seemingly separate roles may actually converge into one coherent anti-cancer mechanism of action as more research is done. Astrocytoma cells have been shown to proliferate in the presence of a strong pro-oxidant, but their proliferation was inhibited by the presence of NAC. 5 Another study suggests that an inverse correlation exists between cellular lipid peroxidation and neoplastic transformation. 6 The authors postulate that restoration of adequate antioxidant status in a cancer cell may modulate re-differentiation within the cell and inhibit cellular proliferation. Other more common antioxidants are also utilized in R-A Therapy. These include vitamins A, C, and E. A study in humans published in 1999 evaluated the roles of both vitamin A and NAC in patients with cancer of the lungs and bronchial systems. 7 A Scandinavian study elucidated the beneficial roles of NAC, and the antioxidant vitamins A, C, and E in retarding the growth and development of colorectal tumors. 8 It is well known that colorectal polyps may transform into colon cancer. The study found that of the 209 evaluated test subjects, 35.9% of the untreated controls developed polyps, whereas only 5.7% of the subjects supplemented with vitamins A, C, and E, developed polyps. A furtherance of this study indicated preliminary data that those subjects who received NAC had a 40% reduction in polyps compared to controls.
Studies showing an effect of diminishing proliferative growth of pre-cancerous lesions such as colon polyps may well also indicate direct anti-proliferative activity by the agent tested. Agents studied may also prove useful to prevent the development of cancer via genetic healing mechanisms that eliminate the cancerous cell during the transformation process, thereby sparing us the development of the mature disease. In a study of people at risk for colon cancer, NAC was shown to decrease the proliferative index. 9 The proliferative index is thought to be a predictive biomarker for the risk of developing a neoplastic disease.
Natural polyphenols are another group of natural substances utilized extensively in R-A Therapy. In the 1800s, homeopathy was the predominant form of medical care administered in the United States. The majority of MDs at that time primarily practiced homeopathy in their medical clinics. Homeopaths of that era cited homeopathic phenol as a leading medicine in cancer care. Modern research is once again bearing out the benefits of natural polyphenols in oncology. Green tea extract is rich in natural polyphenols and is used in RA therapy. A study designed to evaluate and elucidate the cytotoxic effect of green tea polyphenols revealed a decrease in tumor cell viability in the presence of green tea extract and one of its component polyphenols known as epigallocatechin (EGC). 10 The authors stated, “Epidemiological studies suggest that the consumption of green tea may help prevent cancers in humans, and also breast and prostate cancers in animal models are reduced by green tea, and several mechanisms of action have been proposed for these effects.”
Other members of the polyphenol family used in R-A Therapy include butyric acid, phenylic acid, many forms of catechins, carbolic acid, and components of the cruciferous vegetable family. Phenylehtylisocyanate and NAC were both studied to elucidate the anti-cancer role of the polyphenols and other natural components of cruciferous vegetables. 11 The study showed that these natural substances caused cytolysis of human prostate cancer cells when they were exposed to high doses of the agents and growth modulation, which was dose-dependent at lower concentrations. The authors are quoted as stating: “There is growing evidence that thiol conjugates of isothiocyanates present in cruciferous vegetables are effective cancer chemopreventive and potentially active therapeutic agents.” Butyrate was found to induce apoptosis in a cancer cell line normally resistant to undergoing apoptosis. 12 The colon cancer cells were induced to undergo apoptosis induced by TNF-alpha and Fas ligating antibody. Butyrate was also found in the same study to influence reactive oxygen species.
Another two intriguing RATherapy components are alpha-lipoic acid and legitimized ascorbic acid (PC-AS). Lipoic acid, like many medicinal natural substances, seems to have a plethora of potential beneficial mechanisms of action and therapeutic uses. Normally thought of as an antioxidant, lipoic acid may also have a direct effect on the protective genetic apparatus of the cell. In vitro, alpha-lipoic acid exhibits inhibition of neoplasia. 13 The authors of this study stated that “alpha-lipoic acid is a potent thiol antioxidant which has been demonstrated to be efficacious in several oxidative stress models.” Ascorbic acid, also known as vitamin C, has long been highly regarded in alternative cancer medicine for producing therapeutic benefits in cancer patients. A form of ascorbic acid to which lecithin has been covalently bonded revealed even greater effects. 14 Researchers found that PC-AS effectively inhibited murine pulmonary metastases and that the potency of PC-AS was superior to that of ascorbic acid alone. They also showed evidence that NAC produced an additive inhibitory effect when combined with PC-AS.
Methods of inducing genetic healing in cancer, such as R-A Therapy, hold great promise for the future. Evidence of this is found in the recent activity of pharmaceutical firms and biotechnology companies to develop new products based on apoptosis and re-differentiation. One such example is a new drug now in FDA trials called “Aptosyn”. Aptosyn is a man-made molecule derived from the arthritis drug Sulindac, which is found to have a propensity to induce apoptosis in cancer cells. Human clinical trials thus far seem promising. Genetic healing in cancer involves many healing mechanisms which may reasonably be referred to as “self-healing” by the cancer cells themselves. It is probable that adding genetic healing mechanisms such as those found in R-A Therapy to other anti-cancer therapies will yield a far greater therapeutic benefit to patients than has thus far been achieved in oncology.
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