| Research Article |
Open Access |
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| Mushtaq Ahmed1, Muhammad Imran Khan1, Muhammad Rashid Khan2, Nawshad Muhammad1, Amin Ullah Khan1 and Rahmat Ali Khan1* |
| 1Department of Biotechnology, Faculty of Biological Sciences, University of Science and Technology Bannu, Khyber Pakhtunkhwa, Pakistan |
| 2Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan |
| *Corresponding author: |
Rahmat Ali Khan
Department of Biotechnology
Faculty of Biological Sciences
University of Science and Technology Bannu
Khyber Pakhtunkhwa, Pakistan
Tel: +92 51 90643086
Fax: +92 51 9252087
E-mail: rahmatgul_81@yahoo.com
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| Received January 03, 2013; Published January 26, 2013 |
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| Citation: Ahmed M, Khan MI, Khan MR, Muhammad N, Khan AU, et al. (2013) Role of Medicinal Plants in Oxidative Stress and Cancer. 2:641 doi:10.4172/scientificreports.641 |
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| Copyright: © 2013 Ahmed M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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| Abstract |
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| Cancer is a group of diseases characterized by malignant neoplasm. It is a major public health problem, almost everywhere in the world. There are many types and causes of cancer. Many types of cancer are lethal. Oxidative stress is closely related to various diseases, including cancer. The human body is constantly exposed to free radicals arising from exogenous and endogenous origins, which cause oxidative stress. Oxidative stress may lead to gene mutations, which may affect intracellular signal transduction and transcription factors, leading to carcinogenesis. Antioxidants are protector of the body, preventing oxidative stress, by stabilizing free radicals. Plants are good and cheap sources for the prevention and treatment of oxidative stress and cancer. Natural antioxidant from plants are being used for the treatment of cancer. |
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| Keywords |
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| Anticancer; Medicinal plants; Natural products; Free radicals; Antioxidant; Oxidative stress; Carcinogenesis |
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| Overview of Cancer |
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| The term cancer is used in the medical sciences for the unregulated cell growth. Cancer cells grow in uncontrollable manner, and result in malignant tumors which attack on the nearby parts of the body. The cancerous cell, when spread to other parts of the body through lymphatic or blood stream, is called metastasis. All the tumors are not cancerous in nature; some of them are benign, which do not invade the nearby tissue, and do not spread to other parts of the body. More than 200 types of cancer have been identified that harm the human body. Various factors have been identified that increase the risk of cancer, such as smoking, exposure to radiation, obesity, lack of physical activity, environmental pollutants and oxidative stress. Cancer caused mutation, which some time results in other diseases. The hereditary role in cancer was identified to be from 5-10%. Cancer can be diagnosed by using the biochemical screening tests and medical imaging. The chemotherapy, radiation therapy and surgery are normal procedures adopted for the treatment of cancer. These procedures either have less or more side effect, while the usage of medicinal plants in the treatment of cancer is safer than usual procedures. |
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| Relation between Oxidative Stress and Carcinogenesis |
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| Active oxygen may cause cancer through two possible mechanisms: gene mutations and the effects on signal transduction and transcription factors. Oxidative stress causes damages to DNA, phospholipids, proteins and carbohydrates on the cell membrane. Oxidation and injury to DNA induce genetic mutation. The presence of free radicals may enhance the mutation of some genes. |
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| Antioxidant Defense System |
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| An antioxidant is “any substance that delays, prevents or removes oxidative damage to a target molecule” [1]. Antioxidants can act by diverse mechanisms in the oxidative sequence. The human body complex antioxidant defense system consists of the dietary intake of antioxidants, as well as the endogenous production of antioxidative compounds, such as glutathione, etc. [2]. Antioxidants can be classified into a number of different groups as enzymatic and non enzymatic strategies. The enzymatic antioxidant involve superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, while non enzymatic antioxidants include the vitamins A, C, and E, glutathione, and lipoic acid, mixed carotenoids, several bioflavonoids, antioxidant minerals (copper, zinc, manganese, and selenium), etc. Antioxidants may work either alone, or in association with each other against different types of free radicals. Vitamin E inhibits the propagation of lipid peroxidation; the combination of vitamin C and vitamin E suppress the formation of hydroperoxide; metal complexing antioxidant such as penicillamine inhibit free redical formation in lipid peroxidation [3]. |
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| Oxidative Stress in the Human Body |
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| Human body is constantly generating free radicals, which causes oxidative stress. Factors such as drugs, pollution, immune responses to viruses, deficiency of natural antioxidants, ultraviolet rays and tobacco destroy the body potential of stabilizing free radicals. In addition to those exogenous sources, endogenous sources of oxidative stress include mitochondria, or microsomes and peroxisomes, and enzyme NADPH. The body has the power to neutralize them, but if there is an imbalance between the free radicals and the ability of the body to neutralize it, it causes oxidative stress. Oxidative stress may cause various problems and diseases such as diabetes, Alzheimer’s disease, Parkinson’s disease, aging and cancer. |
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| Lipid Peroxidation |
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| Oxidative stress causes Lipid peroxidation in cell membranes, determined as free radicals, reacting with polyunsaturated fatty acids. Cell membranes contain polyunsaturated fatty acids (PUFAs) and lowdensity lipoproteins (LDL). They are sensitive to free radicals [4]. The interaction of ROS and lipids consists of three different steps: initiation, propagation and termination. The molecular oxygen reacts with carbon-centered free radicals, and thus, lipid hydroperoxides (LOOH) are formed. LOOH alter the membrane structure and function. |
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| Protein Oxidation |
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| Free redicals cause proteins oxidation. There are various markers of protein oxidation, which include protein carbonyl derivates, oxidized amino acid side chains and formation of advanced glycation end products. In the oxidation process, Protein carbonyl derivates are formed early, and are generated as the peptide main chain as some amino acid side chains that are cleaved (arginine, lysine, or threonine), are oxidized [5-7]. The carbonyl groups are relatively stable [7], and may result in loss of protein function, as well as increased degradation of soluble proteins [5]. Protein oxidation has also been shown to be a chain reaction and may be inhibited by chain-breaking antioxidants [ 8]. Oxidation of proteins may develop some problem, but protein damage can be repaired, and is a non-lethal event for the cell [9]. |
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| Oxidative Damage to DNA |
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| DNA is especially sensitive to damage due to its potential to create cumulative mutations, which may disrupt cellular homeostasis [10]. DNA may be damaged by ROS and cause permanent structural changes in, as base-pair mutations, deletions, insertions, rearrangements and sequence amplification [11]. Continuous oxidative damage to DNA may lead to alterations in signaling cascades or gene expression, and may cause replication errors and genomic instability [10]. |
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| Free Radicals and Formation of Cancer |
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| In recent years, oxidative stress and the mechanisms by which cancer is caused has been extensively studied. Cancer development is a multistage process which involves mutations in critical genes required for maintenance of the cellular homeostasis [10]. Oxidative stress causes initiation, promotion and progression of carcinogenesis [12]. ROS play an important role in the development of cancer. Oxidative damage to DNA or of antioxidant defense systems leads to mutation, activated transcription factors, modification of gene expression and chromosomal aberrations, processes which have been described as the agents of progressions of cancer. |
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| Inflammation also causes DNA mutaion [13]. 25% of all cancers in the world is due to chronic inflammation due to infection or injury [ 14]. Various chemicals such as chlorinated compounds, metal ions, aromatic hydrocarbons and some peroxisome proliferators have been shown to induce oxidative stress, which damages the DNA. They may, therefore, partly account for the development, especially of workrelated cancers. Many cancers are associated with increased production of ROS [12]. |
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| Cancer and Phytotherapy |
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| Natural products, especially plants, have been used for the treatment of various diseases from ancient times. People of Egypt, China, India and Greece have been using terrestrial plants as medicines, and a large number of modern drugs have been developed from them. Medicinal plants have been used in the treatment of many diseases, such as diabetes, obesity and cancer, etc. There are many evidences that the generation of free radicals inside the body cause damages to DNA and lead to the development of cancer, etc., and if these free redicals are neutralized by the antioxidants from different medicinal plants, then it prevents cancer. Several studies have shown that plant derived antioxidant scavenge free radicals and modulate oxidative stress. Free radicals are the cause of many diseases such as cancer, atherosclerosis, diabetes, neurodegenerative disorders and aging; different experimental and clinical studies have proved that higher intake of antioxidant rich food is associated with decreased risk of cardiovascular diseases and cancer. The free radical neutralizing property of several plants have been screened by various researchers. Plants have been used in the treatment of cancer. The National Cancer Institute collected about 35,000 plant samples from 20 different countries, and has screened around 114,000 extracts for anticancer activity. 60% of the commercialy available anticancer drugs are from natural sources. |
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| Treatment by herbal medicines may have some advantages over treatment by single purified chemicals [15]; as hebal medicine are the mixtures of more therapeutic or preventive components, and so might have more activity than single products alone. The antioxidant and anti-tumor effects of extracts from various herbs and medicinal plants have been proved experimentally and clinically. Several in vitro or in vivo studies have proved the anticancer potential of the extracts from several medicinal plants [16-18]. Experimental studies of aqueous extracts from willow (Salix sp.) leaves show prevention of proliferation of cancer cells [18]. Ganoderma lucidum methanolic extracts induced apoptosis in human breast cancer cells Hu et al. [17] and Kao et al. [19] studied that an aqueous extract of Bu-Zhong-Yi-Qi-Tang (a mixture of ten herbs), had the ability to induce apoptosis in hepatoma cells. Most of the plants contain phenolic and flavonoid compounds, which have antioxidant activities, and thus, prevent oxidative stress and cancer [ 20]. |
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| The effect of an aqueous extract of Paeoniae lactiflora were studied on HepG2 and Hep3B hepatoma cells, which showed apoptosis. Yano et al. [21] stated that aqueous extract of Sho-Saiko-To caused inhibition of the proliferation of KIM-1 human hepatoma cells. It was stated by Bonham et al. [16] that PE-SPES (mixture of eight herbs) had been used as a clinical treatment of prostate cancer. Chemical and diferent studies of various extracts from the herbs were found to to be useful in preventing radiation damages and purify blood quality [22,23]. The seeds of Luffa aegyptiaca has the ability to destroy the human metastatic melanoma [24]. |
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| Plant Derived Anticancer Agents in Clinical Use |
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| The anticancer agents, vinblastine and vincristine from the Madagascar periwinkle, Catharanthus roseus G. Don. (Apo-cynaceae), introduced a new era of the use of plant material as a medication for treatment. They were the first agents to advance into clinical use for the treatment of cancer. Vinblastine and vincristine are used in combination with other cancer drugs, for the treatment of various kinds of cancers, including leukemias, lymphomas, advanced testicular cancer, breast and lung cancers. |
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| The isolation of paclitaxel (Taxol®, 3) from the bark of the Pacific Yew, Taxus brevifolia Nutt. (Taxaceae), is another good step in the discovery of natural product drug. Various parts of Taxus brevifolia and other Taxus species (e.g., Taxus Canadensis Marshall, Taxus baccata L.) have been used by several native American tribes for the treatment of various diseases, while Taxus baccata was reported to use in India as a medicine for the treatment of cancer. The paclitaxel was clinically introduced to the US market in the early 1990s. Paclitaxel is active against a number of cancer types, for example: ovarian cancer, advanced breast cancer, small and non-small cell lung cancer. Camptothecin was isolated from the Chinese ornamental tree, Camptotheca acuminate Decne (Nyssaceae), the clinical trials in the 1970s dropped it because of severe bladder toxicity. Derivatives of camptothecin, Topotecan and irinotecan, are used for the treatment of ovarian and small cell lung cancers, and colon cancers, respectively. |
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| Conclusion |
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| Free radicals are the cause of oxidative stress, which may causes injury to cells, gene mutation, and may lead to cancer. Oxidative stress causes cancer, by the interaction with intracellular signal transduction and transcription factors, directly or indirectly. Medicinal plants are main sources in healing of the cancer around the world. This property of the plants is because of the presence of potent anti cancer substances. Medical plants treatment of cancer is prevalent, especially in our country where resources are limited. Several medicinal plants have been known to cure and control cancer. Most of the medications used word wise contains herbal product, with no side effects. |
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