Antitumor Effects Of Chromones

About 12,820 new cases of invasive cervical cancer will be diagnosed in America every year (5). This is out of the 1,685,210 people diagnosed with cancer every year. About 39.6% of the US population will contract cancer in their lifetime (10). With so many people affected by cancer, it is beneficial to understand how cancer works. However, cancer is a very complex disease that scientists are still trying to understand themselves. Moreover, cancer can be a very frightening disease because of its difficulty to treat, and its lethality. Understanding the pathology and history of cancer can be beneficial to help understand the inevitable cancer diagnosis of yourself or a loved one.

Cervical cancer is the second foremost occurring cancer in women after breast cancer. Cervical cancer is a sexually transmitted disease caused by the human papillomavirus, or HPV. Infection by HPV typically occurs in the early years of sexual activity according to the World Health Organization (WHO), but it can take up to a full twenty years for it to develop into a full-blown malignant tumor. Scientists believe that for all intents and purposes all cervical cancer cases are caused by infection with a few types of cancer. Great strides have been made in recent years in the development of a vaccine to treat the cervical cancer. Scientists have cultivated a prophylactic vaccine that would protect against the human papillomavirus. HPV's

Immunotherapy is the most promising new cancer treatment since the development of chemotherapies in the 1940s and thus has the potential to produce a plethora of effective treatments for future patients fighting the disease for decades to come. Essentially, these drugs work by targeting the host immune system, instead of the tumor, in order to attack cancer cells harder and smarter than through previous treatments (Kohrt et. al., 2016). The immune system recognizes the tumor cells as foreign, triggers an immune response, and then promotes tumor cell death or growth inhibition (Berman and Simone, 2016). When considering all of the involved immune cells, cytokines, and other immune factors that play a role in the function of the immune system, it is clear that there is a potential to develop many novel anti-tumor strategies for the future (Thara & Barzi, 2015).

NAD(P)H quinone-acceptor oxidoreductase (NQO1) is an enzyme that is responsible for reducing quinones to hydroquinones in the cell. This minimizes the generation of reactive oxygen intermediates by redox cycling and also depletes the intracellular thiol pool. NQO1 consists of 2 catalytic sites which uses NAD(P)H as an electron donor in order to form hydroquinones. The metabolic activation of a variety of quinone-based anticancer agents occurs, in part, as a result of the bioreductive activation by NQO1. Its association with p53 gene results in proteosomal degradation in the nucleus, thereby broadening the cyto-protective role far beyond

E5 is a protein that alters the activity of cell cycle regulators. The phenotype of the cell changes when E5 is expressed. E5 acts at the early stage during carcinogenic progression; research has revealed that E5 is extinguished by integration of the viral genome during the progression to cervical cancer. E5 contributes to cancer development significantly through its mechanism of immune avoidance. As illustrated on figure 1, research suggests that it does so by interacting with B cell receptor-associated protein 31(BAP31). This interaction, labeled #1, induces loss of the surface MHC I expression in infected cells and prevents presentation of viral antigen to effector T-cells. Another mechanism can be observed on figure 1, marked #2. E5 also enhances the actions of E6 and E7 by modulating the transit of signaling proteins through the endoplasmic reticulum. Specifically, E5 interacts with the vacuolar H-ATPase. This interaction promotes recycling of the receptors on cell surface, resulting in constant signaling of epidermal growth factor receptor (EGFR). Increased EGFR signaling leads to activation of MAPK pathway. The MAPK pathway, in

Cancer is the uncontrolled growth of cells, and is a major cause of death throughout the world. The development of cancer chemotherapeutics began in the 1940s [Shewach, D. and Kuchta, R, 2009] and very early drugs were based on nitrogen mustards, agents similar to mustard gas. Sulphur mustard gas was used as chemical warfare in World War I (WWI), and this led to new approaches for cancer therapeutics. These traditional chemotherapeutic compounds however, can attack cell division in a cancerous, as well as a normal cell, as tumour and normal cells share the same DNA. This leads to several serious side effects. Newer chemotherapeutics, such as the use of monoclonal antibodies, target specific differences between tumour and normal tissue, and therefore do not exhibit such toxicities [Shewach, D. and Kuchta, R, 2009]

In spite of all the achievements and advances in the medical field, cancer stays as one of the leading causes of death worldwide. Cancer is an umbrella term for groups of diseases that are all characterized by uncontrolled growth of abnormal cells [1]. These abnormal cells are cells that are either mutated or damaged in such a way that natural mechanisms for checking cell growth are no longer efficient for containing their growth. If these unusual cells are allowed to multiply unchecked, severe health issues will arise possibly leading to death. Cancer can result from both external factors including tobacco usage, virus infections, chemicals, and radiation, as well as from internal factors such as hormones and inherited mutations [1].

In addition to the absence of DNA-reactivity, such carcinogens have been demonstrated to exert other primary cellular effects in their target tissues that could account for their carcinogenicity (Klaunig et al, 2000). Effects of this type include neoplasm promotion, cytotoxicity and increased cell proliferation. In the endocrine and immune systems, chemicals affecting function of these tissues can lead to tumor development (Capen,

Treatment of F344 rats with methapyrilene caused a marked decrease in the trimethylation of histone H3 lysine 4 (H3K4me3) and H4 lysine 20 (H4K20me3), and acetylation of histone H3 lysine 9 (H3K9ac) and H3 lysine 56 (H3K56ac) in the livers. Exposure to usnic acid resulted in a minor reduction of H3K4me3 and H3K9ac only. No histone modification changes were found in the livers of rats treated with aristolochic acid. Also, none of the chemicals caused histone modifications in the kidneys. The methapyrilene-induced hepatic histone modifications were accompanied by a reduced expression of chromatin-modifying genes responsible for the modifications, including histone methyltransferases Suv4-20h2 and Kmt2a, histone demethylase Kdm5b, and histone acethyltransferase Ep300. The results indicate that organ specific carcinogen-induced histone modifications changes may have significance in the carcinogenic process and in carcinogen hazard

Breast cancer is one of the leading causes of high mortality and morbidity in women population worldwide. Up to date, no effective breast cancer treatment has been developed and this has motivated academic scientists for the quest for alternative drugs and the discovery of drug targets. Increasing evidence suggests that carotenoids, which are micronutrients in fruit and vegetables, reduce breast cancer risk [1]. Previous findings suggest a protective role of α-carotene, β-carotene, lutein/zeaxanthin and lycopene in breast cancer risk [2, 3]. Lycopene, a known major carotenoid detected in human plasma, is known to hold the most robust anticancer and chemopreventive properties as demonstrated in clinical trials and animal models of various cancers including mammary cancer, prostate cancer [4] and brain cancer. In vitro and in vivo studies have reported that lycopene prevents the growth of different cancer cells of different organs and inhibits chemically induced carcinogenesis in animal models. Although the excellent antioxidant property of lycopene is most likely the basis for its preventive role toward cancer, the direct anticancer activities of lycopene through multiple mechanisms are disclosed, including regulation of growth factor signaling, cell cycle arrest and/or apoptosis induction, and changes in antioxidant and phase II detoxifying enzymes. The anti-inflammatory activity of lycopene is also considered as an important determinant that suppresses the

5-Azacytidine is a chemical analogue of cytidine, a nucleoside present in DNA and RNA with antineoplastic activity. It is sold under the brand name Vidaza. The drug was first synthesized in Czechoslovakia as potential chemotherapeutic agents for cancer. It is an inhibitor of DNA methylation and was approved by the US FDA for the treatment of Myelodysplastic syndromes (MDS) in May 2004. MDS are diseases caused by abnormalities in the blood-forming cells of the bone marrow, which result in low production of healthy blood cells. Cytotoxic effect is exerted on rapidly dividing cancerous cells by the drug. This restores the normal function of genes to control proper cellular differentiation and proliferation. The systematic (IUPAC) name of this drug is 4-amino-1-B-D-ribofuranosyl-1, 3, 5-triazin-2 (1H)- one and the molecular formula is C8H12N4O5. (1)

The mitotic spindles are predominately found in the metaphase stage of the cell cycle and as such it is targeted by vincristine. Vincristine binds and crystallizes microtubular protein to cause an arrest of cancer cells undergoing division and thus apoptosis. Vincristine is specific for rapidly dividing cells and cancer cells are examples of such cells. Furthermore, it is important to note that vincristine have side chain which are responsible for its anti-cancer effect. Two of such side chains are the acetyl and the hydroxyl. In animal studies it is observed that the hydrolization of the acetyl group and the acetylated of the hydroxyl groups will obliterate the anticancer potential of vincristine. This is because modification of the molecules will wholly change the structure of vincristine. The discovery of pharmacological compounds from plants has been a great achievement in the synthesis of life-saving therapeutic agents. Unfortunately, there is no analogue of

The International Agency for Research on Cancer (IARC), recognized that HPV types 16 and 18 are carcinogenic in humans, in addition, HPV is strongly associated with the development of OPSCC. HPV-16, is believed to be the risk factors for a subset of HNSCC and the most strongly associated with oropharyngeal squamous cell carcinomas (OPSCC). HPVs are divided into cutaneous and mucosal types, based on their tissue tropism, in addition they are divided into low- risk and higher-risk types of HPV, HPV types 6 and 11 are benign and mostly found in oral squamous papillomas and common warts, meanwhile, HPV types 16 & 18 are high-risk and integrated into the host cell of the DNA in malignant lesions. Furthermore, More than 50% of the cancers are found to harbour HPV 16 DNA, and it is considered as a hallmark of malignant transformation. (Krueger H 2010).

According to the National Institutes of Health, in 2016 more than 595,000 people died from cancer, and the US is projected to spend more than $150 billion in the treatment of cancer by 2020 (“Cancer Statistics”). Many of us know a friend or loved one who was killed by a form of cancer, and we may know someone fighting the disease right at this very moment. For this project, I wanted to look at the chemical reasons for why cancer forms, how it grows in the human body, and what can be done to stop it. While scientists are still learning about cancer and its effects, there is a lot of scientific evidence that points to free radicals as one of the

Since I began studying pharmacological treatments and drugs more deeply in the last two years I got to be more convinced by the fact that despite the great benefit that drugs provide including: reducing mortality, morbidity and increasing the quality of life and productivity, there are growing negative impacts that those drugs can cause including: adverse effects, interactions with other drugs or food and resistance! Thus, certainly even for anticancer drugs that showed phenomenal transformation in cancer management, unfortunately chemoresistance has been developed which represents the main reason behind chemotherapy failure in the most common types of cancer such as: lung, colon, and breast; it’s considered to be a major