Sufiyan, N (2016) Evaluation of Anticancer Activity of Ethanol Extract of Pterocarpus Marsupium ROXB. Bark against Ehrlich Ascites Carcinoma (EAC) Bearing Swiss Albino Mice. Masters thesis, J.K.K. Nattraja College of Pharmacy, Komarapalayam.
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Abstract
AIM AND OBJECTIVE OF THE STUDY: Since pre-historic days attempts are being made to find out suitable drugs from natural sources for treatment of different diseases. The rational approaches, experience of folk medicine provide a valuable approach in the search for the development of new and useful therapeutic agents. Gradually keeping in pace with the scientific interpretations of the drug actions, the causes of the diseases, and the development in the field of chemistry and technology, intensive efforts are being directed towards the design and synthesis of new drugs. More recently a study by the World Health Organization (WHO) has shown that about 80% of the World‟s population still relies on traditional medicine. This is of interest to a natural product chemist for many reasons. There is the possibility that the herb used in the traditional medicine is harmful to the patient, in which case the treatment may do more harm the good. Conversely, there is the possibility that the herbs used are not effective at all. That may not be of concern for minor ailments, but in more serious cases an ineffective treatment could result in the death of the patient. Hopefully, however, the herbs used are effective. If that is the case then investigation of that remedy could be of benefit to the remaining 20% of the World‟s population. Natural products still play a very important role in the medicine of the remaining 20% of the world‟s population. Between 1983 and 1994, 41% of new approved drugs have natural products as their source. This percentage becomes even higher when one examines anti-infective and anticancer compounds. For both classes, the percentage of drugs with natural products as their source increases to over 60%. Because natural products are most important in the areas of anti-infective, antioxidants and anticancer agents, some of the important contributions to these drug classes are worth closer inspection. In particular the anticancer drugs will be examined as that is the area of our research. Cancer is a multifactorial, multifaceted and multimechanistic disease requiring a multidimensional approach for its treatment, control and prevention. Cancer involves fundamental biological processes concerning disorganised cell replication, cell death and disorganization of organ structure. The annual estimates of cancer for the year 2001 in India is 0.98 million and the annual mortality in 2000 is 0.7 million. The incidence of cancer is on the rise, with multiple risk factors that involve interplay between genetic and environmental components. The aim of the research is to find out new anticancer drugs from indigenous plants which are potent and nontoxic agents. These plants are traditional medicinal plants. Their chemical characterization, mode of action and toxicity studies are yet to be established. Present project deals with phytochemical and pharmacological evaluation of of ethanol extract of Pterocarpus marsupium Roxb. bark with special reference to in-vitro antioxidant studies (DPPH, ABTS, Nitric oxide and hydrogen peroxide) and in vitro cytotoxicity (MTTS) studies. Normally herbal products are free from side effects/adverse effect and they are low cost medicines, which will be beneficial for the people of this country. Keeping this in view, we have selected two plants from the Kolli hills, Namakkal District of Tamil Nadu which are used by the tribes for the treatment of different types of diseases. The main objective of this work is to develop potent anticancer agent having no minimum side effects from indigenous plants for the therapeutic management. DISCUSSION: The present study was carried out to evaluate the anticancer effect of EEPM in EAC bearing mice. The EEPM-treated mice, at the dose of 100 and 200 mg/kg, significantly increased the survival time, inhibited the tumor volume, packed cell volume, tumor cell count and brought back the hematological parameter to more or less normal levels. The extract also restored the hepatic lipid peroxidation and antioxidant enzymes such as a glutathione content, SOD, and catalase (CAT) in tumor bearing mice to near normal level. In EAC bearing mice, a rapid increase in ascites tumor volume was noted. Ascites fluid is the direct nutritional source for tumor cells and a rapid increase in ascetic fluid with tumor growth would be a means to meet the nutritional requirement of tumor cells105. Treatment with EEPM inhibited the tumor volume, tumor cell count, and increased the percentage of tryphan blue positive stained dead cells in tumor bearing mice. The reliable criteria for judging the value of any anticancer drug are the prolongation of the life span of animals.106 The EEPM treatment decreased the ascetic fluid volume, viable cell count and increased the percentage of life span. It may be concluded that EEPM may act by decreasing the nutritional fluid volume and arresting the tumor growth, increases the life span of EAC bearing mice. Usually in cancer chemotherapy the major problems that are being encountered are myelosuppression and anemia.107,108 The anemia encountered in tumor bearing mice is mainly due to reduction in RBC or hemoglobin percentage, and this may occur either due to iron deficiency or due to hemolytic or myclopathic conditions109. Treatment with EEPM restored the hemoglobin content, RBC and WBC count more or less to normal levels. This indicates that EEPM may possess protective action on the hematopoietic system. Lipid peroxidation, an autocatalytic free radical chain propagating reaction, is known to be associated with pathological condition of cell. Malondialdehyde (MDA), the end product of lipid peroxidation, was reported to be higher in cancer tissue than in non- cancerous organ109. A major target of reactive oxygen species (ROS) is cell membrane, due to the high content of polyunsaturated fatty acid. ROS mediated lipid peroxidation causes damage to cellular DNA, membrane structure and inhibition of functions of several enzymes and alteration in the immune system. In cancer, enormous production of free radicals in the system has been reported. A close relationship between free radical activity and neoplastic transformation has been shown. Antioxidants play a vital role in scavenging reactive oxygen species and protect the cells from oxidative damage. In EAC bearing mice the level of lipid peroxidation was significantly increased. Administration of EEPM at the dose level of 200 mg/kg animal groups significantly inhibited as the elevated level of lipid peroxidation as compared with control animals. Glutathione (GSH), a potent inhibitor of neoplastic process plays an important role in endogenous antioxidant system that is found particularly in high concentration in liver and it is known to have key function in protective process. Excessive production of free radicals resulted in oxidative stress, which leads to damage of macro molecules for example, lipid peroxidation in vivo.110 It was also reported that the presence of tumors in the human body or in experimental animals is known to affect many functions of the vital organs, especially in the liver, even when the site of the tumor does not interfere directly with organ function .111 The present study indicated depletion in GSH contents in the EAC control group, which was found to be significantly increased following treatment with EEPM in comparison to control groups and this may be attributed to the antioxidant and free radical mechanism. The functions of the SOD and CAT activities, present in all oxygen metabolizing cells, is to provide a defence against the potentially damaging reactivity of superoxide and hydrogen peroxide. Inhibitions in the activities of SOD and CAT as a result of tumor growth were also reported112. Similar findings were observed in the present investigation with EAC bearing mice. The administration of EEPM at the doses 100 and 200 mg/kg significantly altered status of SOD and CAT levels in a dose dependent manner as compared with control. Cells are also equipped with enzymatic antioxidant mechanisms that play an important role in the elimination of free radicals. SOD, CAT and glutathione peroxides are involved in the clearance of superoxide and hydrogen peroxide (H2O2) radicals. SOD catalyses the diminution of superoxide into H2O2, which has to be eliminated by glutathione peroxidase and or catalase113. In correlation, it has been reported that a decrease in SOD activity in EAC bearing mice which might be due to loss of Mn2+ containing SOD activity in EAC cells and the loss of mitochondria, leading to a decrease in total SOD activity in the liver.114 A small amount of catalase in tumor cell was reported.115 The inhibition of SOD and CAT activities as a result of tumor growth was also reported.114 Similar findings were observed in the present investigation with EAC bearing mice. The administration of EEPM at different doses significantly increased the SOD and CAT levels as compared to that of DAL control group. It was reported that plant derived extracts containing antioxidant principles showed cytotoxicity towards tumor cells116 and anticancer activity in experimental animals.117 Anticancer activity of these antioxidants is either through induction of apoptosis118 or by inhibition of neovascularization.119 The implication of free radicals in tumors is well documented.120, 121 The free radical hypothesis supported the fact that the antioxidant and anticancer principles present in the extract.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | Anticancer Activity ; Pterocarpus Marsupium ; ROXB ; Ascites Carcinoma ; EAC ; Swiss Albino Mice |
| Subjects: | PHARMACY > Pharmacology |
| Depositing User: | Ravindran C |
| Date Deposited: | 05 Jan 2018 05:38 |
| Last Modified: | 05 Jan 2018 05:38 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/4944 |
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