Role of Gluthathione Pathway in Discovering Anticancer Compound

However, the majority of known anti-cancer drugs target normal cells as well. Methotrexate, formerly known as amethopterin, is an antimetabolite used in the treatment of some forms of cancer (Shacter and Law, 1956). It inhibits the function of dihydrofolate reductase (DHFR) by tightly binding to the enzyme. Following this slow interaction between methotrexate and DHFR, an enzyme-NADPH-inhibitor complex is formed (Stone et al., 1984). Therein, DHFR is rendered unable to catalyze the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate (Anderson, 2017). Tetrahydrofolate is an important methyl group shuttle in the de novo synthesis of purine and pyrimidine nucleotides and some amino acids (Barbara and Hiroshi, 2002). Therefore, eliminating it from cells is a good therapeutic strategy against cancer cells, as it would limit the de novo synthesis of purines and pyrimidines (Lane and Fan, 2015). Inhibiting the function of DHFR by its competitive inhibitor methotrexate is one such good therapeutic strategy, as it would disable DHFR from converting dihydrofolate into tetrahydrofolate. However, some types of cancer cells had acquired some forms of resistance against methotrexate (Hans et al., 2011). Equally important, methotrexate should be administered in well established low doses, because it affects

While Season felt completely broken-down, she knew that she had no choice but to bring her background in nutrition to her own home. To build Kicker’s immunity Season implemented The Ketogenic Diet. The human body produces cancerous cells daily, so building a strong immunity is imperative when fighting off cancer cells and the harsh chemicals from treatment. The Ketogenic Diet is a new cancer treatment, which is free, with virtually no side effects. It can also be conjoined with other cancer treatments. The diet involves cutting carbohydrates, beginning with the worst carbohydrate of all, sugar (Johnson L, 2013). It is a high-fat, adequate-protein, low-carbohydrate diet. The diet forces the body to burn fats rather than carbohydrates. Normally the carbohydrates contained in food are converted into glucose, which are then transported around the body. However, if there are little carbohydrates in the diet then the liver converts fat into fatty acids and ketone bodies. Ketone bodies are water molecules that are produced when the body is consuming very little food, which mimics fasting. Cancer is an obligate glucose metabolizer because it fuels on sugar. One’s normal cells have the metabolic flexibility to adapt from saving glucose by using ketone bodies (Johnson S, 2014). This addressed that because cancer

The anti-apoptotic mutations related to cytochrome c are not the only mechanisms acquired by cells in the development of a tumor. Another important hallmark of cancer is the alteration of cellular metabolism, also known as the Warburg Effect, which demonstrates an increased rate of glycolysis despite the presence of oxygen in tumor cells (Hallmarks). Due to the unlimited and uncontrollable division by tumorigenic cells, the Warburg Effect confers growth advantages compared to non-proliferating cells because it promotes the uptake of glucose, it produces less reactive oxygen species (ROS), and it generates ATP more rapidly than oxidative phosphorylation, all of which are considered to facilitate rapid growth and survival (1).

Norcantharidin (NCTD), the demethylated analogue of cantharidin, has been used to treat human cancers in China since 1984. It was recently found to be capable of inducing apoptosis in human colon carcinoma, hepatoma and glioblastoma cells by way of an elusive mechanism.1 Norcantatharidins and their analogues are synthetic anticancer agents which have been used in various different procedures for the inducing growth arrest and apoptosis of tumour cells and also provide therapeutic and adjuvant therapeutic applications in the treatment of cancer agents.2 This report will discuss the various different NCTD that are currently being studied, highlighting the synthesis of these NCTD and their various biological pathways that are taken in order to inhibit the growth of the correspondent cancer cell. In particular NCTD induced apoptosis of the hepatoma cells will be considered and also highlighting the different views with the synthesis of the particular NCTD and also the effectiveness of the methodology and its observations in response to other NCTD and their mechanism in attacking the hepatoma cell site.

Based on ¨Principles of Pharmacokinetics¨, ¨pharmacokinetics is the study of absorption, distribution, metabolism, and excretion¨ (Ratain 2003). In other words, the drug's pharmacokinetics determines the duration and the intensity of the effect on the body. Absorption rate can be affected by the drug itself, such as: rate of dissolution, lipid solubility, and route (VandeWaa 2016). The absorption process starts by the route of admission, in this case oral. The oral, or by mouth, route of administration for drugs is the most common. When a pill is taken by mouth, it travels down to the stomach, were most pills dissolve. While in the stomach, some kinds of pills are absorbed into the stomach lining, but some move on to the small intestine. Every pill eventually ends up in the bloodstream and circulate through the body to tissues and organs (Howell 2017). Once passive diffusion occurs, the cells absorb the molecules of the medicine. Then, the molecules of the medicine will exit the cells and travel in the bloodstream for the distribution process.

The extracts and polyphenols suppressed cell proliferation, promoted apoptosis, modulated signaling transduction, inhibited cell invasion, and prevented angiogenesis and metastasis in animal models related to multiple types of cancer such as liver, bladder, prostate, intestine, colon, pancreas, and mammary gland in more than one hundred publications (Yang & Wang, 2010; de Moura et al., 2013). Green tea has been studied expansively for its cancer prevention effects which are believed to be associated with green tea polyphenols known as "catechins (-)-epigallocatchin-3gallate (EGCG), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG), and (-)-epigallocatechin (EC)...they each have a level of antioxidants and are strong metal ion chelators, which prevent the formation of reactive oxygen species (ROS)" (Yang & Wang, 2010, p. 931; Ziech et al., 2012). Further research has revealed that high concentration levels are necessary to accomplish this, and adding other agents such as Atrovastatin, a drug used to lower cholesterol, increase success (Yang & Wang, 2010). EGCG has demonstrated the most success because it "serves an antioxidant, or pro-oxidant, and

Within the Brugge Lab, we have investigated the role of various metabolic pathways in cancer including the role of antioxidants within the tumor cell. Although antioxidants were previously believed to scavenge harmful reactive oxygen species (ROS) and provide a protective benefit against cancer, clinical trials have demonstrated that supplementation with antioxidants actually increased prostate cancer incidence among healthy patients. I joined a postdoctoral fellow in the lab to determine whether depletion of glutathione, the major antioxidant within the cell, would put the cell in a sensitive state that made it vulnerable to inhibition of other major pathways. Through our screening effects, we discovered that triple negative breast cancer cells become exquisitely sensitive to treatment with inhibitors of deubiquitinating enzymes through an induction of a proteotoxic stress response. I look forward to sharing these findings with the scientific community as second author on the manuscript currently in preparation.

Cancer is the second most prominent cause of death in the United States. In the year 2016, it is predicted that 595,690 Americans will die from this disease.12 Caner is defined as an uncontrollable division of cells in the body that spreads into surrounding tissue. This rapid division of cells can occur almost anywhere in the human body. The cancer treatments currently available in modern medicine include a combination of chemotherapy, radiation, and surgery. Recently scientists have discovered that there could be another way to battle this epidemic. There proves to be a strong correlation between this rapid cell division that is seen in cancer patients with the metabolism of glucose. Glucose provides the energy needed for these cells to continue to rapidly divide and develop new cells. This could mean that nutrition may be a very valuable weapon in the war against cancer. 5 A high fat, low carbohydrate diet, also known as a ketogenic diet, has been successful in the clinical world for patients with uncontrollable seizures, but it may now pose as a viable resource to assist in cancer recovery. By restricting carbohydrates through diet, thus starving the cancer cell of glucose, we may be able to slow or terminate the spread of these cancer cells. The objective of this paper will be to give a better insight on how a Ketogenic diet may aid in delaying or terminating cancer.

Niosomes can alter the metabolism; prolong circulation and half life of the drug, thus decrease the side effects of antineoplastic drugs. Niosomally entrapped methotrexate and doxorubicin showed beneficial effects over the free drug, such as decreased rate of proliferation of the tumor and higher plasma levels accompanied by slower elimination (9).

Selenium is an essential trace element found in the body that works in conjunction with other vitamins to support the powerful detoxification process. When combined with Vitamin E, Selenium can help prevent oxidative stress from occurring in the body which is crucial in the prevention of many diseases such as heart disease and cancer. According to Dr. Mandal (2015), "Oxidative stress is essentially an imbalance between the production of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralization by antioxidants." Selenium goes to work in the body as a powerful antioxidant, and it is required for the production of Glutathione, which is a key antioxidant in our bodies. Antioxidants are important in keeping the body healthy by fighting off the free radicals that our cells are exposed to on a daily basis.

Radiation therapy is the ionization of atoms in tissues resulting in formation of highly reactive radicals in a well-defined, restricted volume (1). In other words, ionizing radiations are used to eradicate tumors and at the same time preserve structure and function of normal tissue. A limitation is prevented from being a problem. If bone marrow or neuronal cells are destroyed or injured, they do not regenerate. However, with radiation therapy, these cells are often saved from injury or destruction, unless the tumor is infecting bone marrow or neuronal cells. Today, radiation therapy is the most popular type of cancer therapy in use. It is used to treat one-half to two-thirds of all cancers, which translates to more than ten percent of the population

Depending on the type of cancer and the stage of cancer the effects on the human body can vary. In general cancer can “block channels in the body and stop particular body systems from functioning properly” (UK). Cancer biggest effect on the human body is the disruption of the body’s ability to maintain a stable internal environment, also known as homeostasis. This disruption of homeostasis leads to the failure of certain body systems and organs, this will eventually lead to death. For example, “bone cancer may interfere with calcium homeostasis” (Mader and Windelspecht), which can cause an imbalance in red blood cells production in the body. Red blood cells carry oxygen throughout the body; without oxygen cells and organs with cease functioning. If organs like the pancreas and liver develop cancer homeostasis can be seriously compromised. The pancreas and liver “controls the level of chemicals and other bodily fluids in the body” (Mader and Windelspecht), so when cells in these organs become cancerous the chemical levels become imbalanced and can cause some organs to fail and body systems to function improperly. In the case of tumor growths, pathways, passages and cavities in body systems like the respiratory, cardiovascular and lymphatic system can be blocked and cause these systems to be unable to carry out their specific

Selenium protects from cancers, for example, prostate, colorectal and lung cancers in specific. This is important for generation of enzymatic reactions that are essential for the production of Apoptosis (automatic cell death). This process ensures the destruction of the harmful cellular colonies of cancer cells without damaging the healthy cells. Being an antioxidant, this mineral helps prevent the cell and DNA damage by free radicals that may cause the production of cancer cells. Selenium also boosts the repairing of DNA and prevents its mutation. One of the essential ways that the mineral is effective in cancer prevention is its ability to enhance the release of glutathione, an essential anti-cancer enzyme.

The elimination of foreign compounds like drugs and toxins from the body is essential since it is designed to protect the body against the potential toxicities that enter the system from the food ingested or through other means. When the food is consumed it is broken down in the stomach, absorbed by the small intestine and thereafter taken to the sliver where detoxification takes place. Therefore metabolism of these foreign compounds is important for life since it allows organisms to neutralize and eliminate foreign substances that would otherwise cause an interference with chemical processes that keep the organism alive. Within the liver there are two main types of metabolism that deal with the foreign objects and a third that deals with their transport. These are phase 1 metabolism, phase 2 metabolisms and phase 3. This paper looks at the types of phase 1 reactions of the metabolism of foreign substances (Williams, 1999).

Furthermore, the antioxidant effects of resveratrol could contribute to its anticancer properties it is because ROS which damaging DNA and other macromolecules can contribute to the initiation and progression of cancer.(13)