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Cancer is the second leading cause of death globally and has been predicted to reach about 24 million in the next two decades (Are et al., 2017). A major part of cancer treatment involves cytotoxic drug therapies, which may lead to secondary health problems such as cardiomyopathy, ischemia, and dysrhythmias (Siegel et al., 2012). Lung cancer is one of the most lethal forms of cancer and is estimated to be responsible for about 28% of the cancer related deaths (Rawat et al. 2009; Iqbal et al., 2017). Moreover, an estimated 2,22,500 new lung cancer cases have been reported in 2017 (Iqbal et al., 2017). In India it accounts for about 6% of the total cell deaths with 78.8 deaths/ Lakh in males and 71.8 deaths/ Lakh in females (Rai et al., 2017). Further, lung cancer can be small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) type, where majority of the cases are of NSCLC (92%) type (Noronha, et al., 2012; Rai et al., 2017).
Major causes of lung cancer include smoking, indoor air pollution, occupational exposure to carcinogens (such as arsenic, asbestos, beryllium, cadmium, chromium, diesel exhaust, nickel, silica), dietary factors and genetic predisposition (Wingo et al., 1999; Behera and Balamugeh, 2004; Driscoll et al., 2005). Most common management strategies for lung cancer include surgery, radiotherapy along with chemotherapy. During the early stages of NSCLC, surgery is the most feasible choice of treatment among others (Behera and Balamugeh, 2004). Presently various chemotherapeutic agents are available commercially such as Gemeitabine, Docetaxel, Paclitaxel, Vinorelbine, Topotecan, Irinotecan, carboplatin and Oxaloplatin (Kusari et al., 2009; Pimentel et al., 2011; Iqbal et al., 2017). These drugs are reported to increase survival of the cancer patient for upto one year. However, major limitation of chemotherapy in India scenario is the number of therapy dropouts due to drug related side effects or cost, which lead to development of resistant cancers. Moreover, tumour heterogeneity and increased drug resistance may also cause severe complications during cancer treatment (Goyal et al., 2017). Therefore, the use of novel and more potent anti-cancer agents is the need of the hour. Due to these limitations, a paradigm shift has occurred from synthetic compounds to active compounds derived from natural sources, as an approach towards alternative medicines.
A constant search for drug alternatives has led to discovery and development of novel bioactive compounds with therapeutic potential from natural sources such as animals (majorly marine), plants and microorganisms. Compounds such as vinblastine, taxol, camptothecin, podophyllotoxin, topotecan and vincristine from these sources are extra-nutritional metabolites exhibiting antibacterial, antifungal, antioxidant and/or anti-cancerous properties (Cragg and Newman, 2004). However, plant and animal extracts are complex mixture of compounds and extraction of a single metabolite can be difficult and time consuming. On the other hand, synthesis of bioactive compounds is dependent on parameters such as specific developmental stage, nutritional availability, environmental or stress conditions, which may sometime be tedious to identify and maintain in vitro (Aly et al., 2010; Chandra et al., 2012; Dudeja and Giri, 2014). Due to these limitations, exploring microorganisms is generating interest as a prospect of easily renewable, inexhaustible and cost effective source for bioactive compounds.
Extraction of metabolites from microbes is relatively less tedious, easy to scale up and harvest, thereby facilitating decline in the overall production cost in commercial system. The extraction of the microbes from the plants is less invasive technique as only a small amount of the plant part can be used. By directing the changes in culture conditions, various biosynthetic pathways of microbes can be optimized to produce a derivative of the desired compound. This is an important application for utilizing microbes to produce natural compounds with improved affinity towards the target cells and efficacy. Microorganisms that colonize intra and/or intercellular locations of the plants, without causing any pathogenicity are known as endophytes (Pimental et al., 2011). These endophytes are associated with both aboveground as well as belowground plant parts playing an essential role in plant functioning and fitness. They are chemical synthesizers residing within the plants and produce metabolites such as alkaloids, flavonoids, phenolics, tannins, steroids, quinones, chinones, benzopyranones, xanthones, terpinoids and teralones, which possess medicinal properties (Schulz et al., 2002; Strobel and Daisy, 2003).
Furthermore, there have been reports that endophytes produce the same bioactive metabolite as their host plant due to their survival adaptation in between plant interstitial tissues (Kharwar et al., 2011; Dudeja and Giri, 2014). In order to extract a plant metabolite, the plant material may be required in bulk quantities. Therefore, if endophytes secrete the same compound as the plant, using endophytes would prove to be a more promising approach because the plant itself will not be harmed and the microorganisms can be cultured in bulk. Therefore, the practical advantages of using microbes are ease of storage, up-scaling and perpetuity.
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