Biological Causes of Cancer and Effects

Biological Causes of Cancer and EffectsCancer refers to a set of diseases characterized by the uncontrolled proliferation of prison cellular telephones into a different form against the normal complement of the organism (Kufe Holland, 2003). thither are two types of tumors one is unremitting proliferation of crabby person cells develops into tumor tissues and may multiply crossways to other organs via circulatory dodges resulting in metastasis cognise as malignant tumors and second one those without malignant properties, which are self-limiting, noninvasive and do not metastasise, known as benign tumors. Around 90% of deaths from cancer are due to the metastases (Box Html, 2008).Cancer may concern humans of all ages. According to figures from World health Organisation (WHO), cancer is the second most mortal disease after cardiovascular diseases. In 2010, around 5.5 million people in India were died due to cancer. 71% cancer deaths occurred in both men and women aged of 30-6 9 years. The three most common fatal cancers were oral (including lip and pharynx), stomach, and lung (including trachea and larynx) in men, and cervical, stomach, and breast in women. About 30% of cancer deaths are due to high body mass index, low fruit and vegetable intake, lack of physical activity, tobacco and alcoholic drink use. Hence, the medical of necessity for cancer remain one of the most demanding areas in scientific research (Dikshit et al., 2012 Ferlay et al., 2007).Cancers are first and foremost an environmental disease with 9095% of cases due to modification in lifestyle and environmental factors and 510% due to genetics mutation (oncogenes, tumour suppressor genes and DNA jam genes). Cancer is caused by physical carcinogens (ultraviolet and ionizing radiation), chemical carcinogens (asbestos, components of tobacco smoke, aflatoxin and arsenic), and biological carcinogens (infections from certain viruses, bacteria or parasites). Common environmental factors leading to cancer death admit tobacco (2530%), diet and obesity (3035%), infections (1520%), radiation, stress, lack of physical activity, and environmental pollutants. These environmental factors cause abnormalities in the genetic material of cells. There are certain risk factors for cancers which consist use of Tobacco, alcohol, unhealthy diet and physical inactivity are the main cancer risk factors worldwide (Rayl and Lewis, 2001 Bahls and Fogarty 2002 Gibbs 2003). continuing infections from hepatitis B (HBV), hepatitis C virus (HCV) and some types of Human Papilloma Virus (HPV) are leading risk factors for cancer in low- and middle-in decrease countries. Cervical cancer, which is caused by HPV, is a leading cause of cancer death among women in low-income countries (Newman and Cragg, 2007).It is very unfortunate condition when cancer has been diagnosed there are a flesh of treatments available. As cancer refers to a class of disease, it is unlikely that one single cure for all forms of cancer is possible (Pazdur, 2001 Illidge, 2008). The most common methods include surgery, chemotherapy (with one or more cytotoxic antineoplastic drugs), radiation therapy (ionizing radiation). There are other methods of treatment such as targeted therapies (monoclonal antibody therapy), immunotherapy (enhancing, or suppressing an immune response) and hormonal therapy (Goldenberg, 2002 Rosenberg et al., 1986 Byar and Corle, 1988). New methods, immunotherapy consume the favour to minimizing the adverse effects, in this targets specific antigen solely expressed by tumor cells, only target cancer and not the healthy cell population.According to a report of World Health Organization, more than 80% of worlds populations depend on tralatitious medicine for their primary health care needs (Farnsworth, 1994 Duraipandiyan et al., 2006). Plants have a long history of use in the treatment of cancer and it is significant that over 60% of currently used anti-cancer agents are come from na tural source. Naturally occurring drugs that are part of the war against cancer include vinca alkaloids (vincristine, vinblastine, vindesine, vinorelbine), taxanes (paclitaxel, docetaxel), podophyllotoxin and its derivative (etoposide, teniposide), camptothecin and its derivatives (topothecan, irinothecan), anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin) and others. In fact, half of all anti-cancer drugs approved internationally were all natural products or their derivatives and were developed on the basis of knowledge gained from small molecules or macromolecules that exist in nature (Cragg et al., 2005 Cragg et al., 1997). In between 2001 and 2005, 23 red-hot drugs derived from natural products were introduced for the treatment of disorders such as bacterial and fungal infections, cancer, diabetes, dyslipidemia, atopic dermatitis, Alzheimers disease and genetic diseases such as tyrosinaemia and Gaucher disease out of these 4 drugs have been approved as anti ca ncer agents. The approved anti cancer agents in 2002 doxorubicin, in 2002 estradiol, in 2004 cholorophyll and l- aspartic acid and taxol nanoparticles in 2005 (Butler, 2005). Three new drugs in any case introduced in 2007 originate from microbial sources for the treatment of cancer is marine alkaloid trabectedin, epothilone derivative ixabepilone and temsirolimus (Newman et al., 2003). Nature is an attractive source of new therapeutic candidate compounds as a tremendous chemical diversity is make up in millions of species of plants, animals, marine organisms and microorganisms as potential anti-cancer agent (Bailly, 2009 Butler, 2004 Bhanot et al., 2011).There were various biological mechanisms for controlling the cancer, out of it programmed cell death and cell cycle inhibition are important one. Apoptosis is the do by of programmed cell death (PCD) that may perhaps occur in multicellular organisms. In distinction to necrosis, which is a form of traumatic cell death that outcome from acute cellular injury, apoptosis generally confers advantages during an organisms life cycle. Biochemical events escort to sign cell changes ( word structure) and death (Furuya et al., 1994). There are numerous pathways and signals lead to apoptosis, but there is only one mechanism that in fact causes the death of a cell (Meikrantz W, Schlegel 1995). Subsequent to a cell receives stimulus, it undergoes planned degradation of cellular organelles by activated proteolytic caspases. A cell undergoing apoptosis shows a distinguishing morphology (Alenzi 2004)The breakdown of the proteinaceous cytoskeleton caused by caspases which shown characteristic cell shrinkage and rounding.The cytoplasm appears dense, and the organelles emerge tightly packed.A process of pyknosis (a hallmark of apoptosis) in which chromatin granule undergoes condensation into compact patches in opposition to the nuclear envelope.The nuclear cover becomes broken down and the DNA inside it is split in a process known to as karyorrhexis. The nucleus breaks into a number of separate chromatin bodies or nucleosomal units as a result of the degradation of DNA.The cell tissue layer shows rasping buds known as blebs.The cell breaks together into several vesicles called apoptotic bodies, which afterward phagocytosed.Figure 1.1 Apoptosis in sequence A) normal resting cell B) cell volume is mixed-up and chromatin clumped C) blebbing process D) chromatin collapsed to the margins of the nuclear envelope E) nucleus clumped into a black hole F) cell breaks down into apoptotic bodies and G) apoptotic bodies ingested by macrophage.Cell cycle consists of two successive periods, that characterized by DNA replication and isolation of replicated chromosomes into two separate daughter cells. The cell cycle divided into five phases G0, G1, S, G2, and M. Cell division, or cytokinesis, occurs by dint of the M (mitosis) phase, and is preceded by a preparative phase, or interphase, that includes G0, G1, S and G 2 (Fig. 2). DNA replication occurs in a specific part of the interphase, the S (synthesis) phase, which is preceded by a open called G1, where the cell prepares for DNA synthesis, and followed by G2, during which the cell prepares for mitosis.Figure 1.2 A diagrammatic view of cell cycle indicating formation of two cells from one cellThe big preponderance of the cells are able to divide but do so only when appropriate to replace damaged or dead cells. In fact, cells in G0 account for the major part of the non-growing, non-proliferating section of the human body, being essentially arrested in their growth. Cells in G0 can often be stimulated to enter the cell cycle by external growth signals such as growth factors and hormones that bind to cell surface receptors and then convey the signal from the plasma membrane to the nucleus, a process known as signal transduction(Sherr, 1994 Ostsubo et al., 1995 Cerveira et al., 2012).The plant Aerva lanata L. belonging to family Amaranthaceae h ave been used for very long times in traditional system of medicine as diuretic and in lithiasis. Besides the traditional uses the plant were reported numerous pharmacological effects viz. diuretic (Udupihille and Jiffry, 1986), anti inflammatory (Vetrichelvan et al., 2000), anti-microbial, cytotoxic (Chowdhury et al, 2002), anthelmintic, demulcent (Pullaiah and Naidu, 2003), nephroprotective (Shirwaikar et al., 2004), anti-diabetic, anti-hyperglycaemic (Vetrichelvan and Jegadeesan, 2002 Deshmukh et al., 2008), expectorant, hepatoprotective (Manokaran et al., 2008), hypoglycemic, anti-hyperlipidemic (Krishnan et al., 2009), anti-parasitic and anthelmentic activities (Anantha et al., 2010), anti cancer activity was carried out against Daltons Ascitic Lymphoma (DAL) cell lines which show significant cancer control of the same (Rajesh et al., 2011). Beside this vast studies were carried out by various researchers to showing importance of Aerva lanata L. which includes finger printing c hromatographic technique analysis of steroids, terpenoids, flavanoids and glycosides (Yamunadevi et al., 2011a Mariswamy et al., 2011a Yamunadevi et al., 2011b Mariswamy et al., 2011b). As per previous studies phytoconstituens possessing anti-oxidant properties are believed to prevent or slow down the occurrence of disease such as cancer.In recent years, a large investigation on different classes of imidazo thiadiazoles has been done. Many of them were found to possess definite pharmacological activity. The fusion of a imidazole ring with a 1,3,4-thiadiazole nucleus give rise to a class of heterocyclic systems containing a bridgehead nitrogen instalment known as imidazothiadiazoles. Imidazo2,1-b1,3,4thiadiazole derivatives were first discovered in the early 1950s and, since then, the research work on heterocyclic system has led to significant developments in their chemistry and biology. The planar and rigid heteroaromatic imidazo2,1-b1,3,4thiadiazole ring system have interesting ph ysicochemical and biological properties, because of the presence of four hetero atom and two condensed heterocycles with different -conjugation. Imidazo2,1-b1,3,4thiadiazoles ring systems have been extensively studied and so far, a variety of biological activities have been reported for a large number of their derivatives such as antitubercular, antibacterial, anticancer, anthelmintic, antifungal, anticonvulsant, anti-inflammatory, analgesic, antipyretic, local anaesthetic, diuretic, antileishmanial and herbicidal activities. In addition, they have been reported to selectively inhibit several therapeutic receptors and enzymes, extending their applications in modern drug design (Jadhav et al., 2008).So the present study was designed to evaluate the cytotoxic potential of the plant Aerva lanata L., isolation and characterization of phytoconstituents as well as preparation of their various saucy derivatives as potential anticancer agents (Khazi et. Al., 2011).