Biological Causes of Cancer and Effects

Biological Causes of Cancer and EffectsCancer refers to a redress of ailments characterized by the uncontrolled proliferation of mobile phoneular phones into a different form against the normal co- position of the organism (Kufe Holland, 2003). thither ar ii types of tumors champion is unremitting proliferation of malignant neoplastic disease carrels develops into tumor tissues and may multiply across to other organs via circulative corpses resulting in metastasis cognise as malignant tumors and second one those without malignant properties, which ar self-limiting, noninvasive and do not metastasise, known as gracious tumors. Around 90% of deaths from crab louse are due to the metastases (Box Html, 2008).Cancer may concern humans of all ages. According to figures from population Health governing body (WHO), crabby person is the second to the graduate(prenominal)est degree mortal disease after cardiovascular diseases. In 2010, around 5.5 million people in India were died due to malignant neoplastic disease. 71% crab louse deaths occurred in both men and women aged of 30-69 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 detractor in women. About 30% of cancer deaths are due to high body mass index, low fruit and vegetable intake, lack of fleshly activity, tobacco and alcohol use. Hence, the medical needs for cancer remain one of the most demanding areas in scientific research (Dikshit et al., 2012 Ferlay et al., 2007).Cancers are first and maiden an environmental disease with 9095% of cases due to modification in lifestyle and environmental factors and 510% due to genetics vicissitude (oncogenes, tumour suppressor genes and deoxyribonucleic acid repair genes). Cancer is caused by somatic carcinogens (ultraviolet and ionizing radiation), chemical carcinogens (asbestos, components of tobacco smoke, aflatoxin and ars enic), and biological carcinogens (infections from certain viruses, bacteria or parasites). usual environmental factors chooseing to cancer death allow tobacco (2530%), diet and obesity (3035%), infections (1520%), radiation, stress, lack of corporal 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). chronic infections from hepatitis B (HBV), hepatitis C virus (HCV) and some types of Human Papilloma computer virus (HPV) are leading risk factors for cancer in low- and middle-in uprise 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 rattling unfortunate condition when cancer has been dia gnosed there are a shape of treatments available. As cancer refers to a class of disease, it is unlikely that one wizard cure for all forms of cancer is possible (Pazdur, 2001 Illidge, 2008). The most common methods involve 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 rescue the advantage to minimizing the adverse effects, in this targets specialised 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 traditional medicine for their primary health care needs (Farnsworth, 1994 Duraipandiyan et al., 2006). Plan ts hand over a long history of use in the treatment of cancer and it is significant that over 60% of currently used anti-cancer movers are come from natural sp sinker. 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 either natural products or their derivatives and were developed on the basis of friendship gained from small molecules or macromolecules that exist in nature (Cragg et al., 2005 Cragg et al., 1997). In in the midst of 2001 and 2005, 23 new 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 cancer agents. The approved anti cancer agents in 2002 doxorubicin, in 2002 estradiol, in 2004 cholorophyll and l- aspartic bitter and taxol nanoparticles in 2005 (Butler, 2005). Three new drugs also introduced in 2007 originate from microbic 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 found 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 apoptosis and cell roll inhibition are important one. programmed cell death is the demonstrate 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 return from acute cellular injury, apoptosis generally confers advantages during an organisms life motor troll. Biochemical events find out to feature article cell changes (morphology) 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 be after 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 ch romatin 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 magnetic core breaks into a number of separate chromatin bodies or nucleosomal units as a result of the degradation of DNA.The cell tissue layer shows uneven 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 baffled 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.electric 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 p hases G0, G1, S, G2, and M. Cell division, or cytokinesis, occurs through the M (mitosis) phase, and is preceded by a preparative phase, or interphase, that includes G0, G1, S and G2 (Fig. 2). DNA replication occurs in a specific part of the interphase, the S (synthesis) phase, which is preceded by a gap 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 vast 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 rate 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 restrain 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. be to family Amaranthaceae have been used for very long times in traditional system of medicine as diuretic and in lithiasis. similarly 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 c ontrol of the same (Rajesh et al., 2011). Beside this vast studies were carried out by various researchers to viewing importance of Aerva lanata L. which includes finger printing chromatographic 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 handsome 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 beachhead nitrogen atom known as imidazothiadiazoles. Imidazo2,1-b1,3,4thiadiazole derivatives were first discovered in the early 1950s and, since then, the research work on hetero cyclic 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 physicochemical and biological properties, because of the presence of quadruple hetero atom and two condensed heterocycles with different -conjugation. Imidazo2,1-b1,3,4thiadiazoles ring systems have been extensively canvass and so far, a variety of biological activities have been reported for a large number of their derivatives such as antitubercular, antibacterial, antitumor, 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-day drug design (Jadhav et al., 2008).So the present study was designed to estimate the cytotoxic potential of the plant Aerva lanata L., isolation and characterization of phytoconstituents as come up as preparation of their various novel derivatives as potential anticancer agents (Khazi et. Al., 2011).