|Year : 2014 | Volume
| Issue : 1 | Page : 34-39
Natural ways to prevent and treat oral cancer
Shweta Danaraddi, Anila Koneru, Santosh Hunasgi, Surekha Ramalu, M Vanishree
Department of Oral and Maxillofacial Pathology, Navodaya Dental College, Raichur, Karnataka, India
|Date of Web Publication||5-Sep-2014|
Department of Oral and Maxillofacial Pathology, Navodaya Dental College, Raichur 584103, Karnataka
Source of Support: None, Conflict of Interest: None
Oral cancer is one of the usual causes of mortality all over the world, with a five-year survival rate of only 50%. Oral cancers are treated primarily by surgery with / without adjuvant radiotherapy and / or chemotherapy. However, there is significant post-treatment morbidity and mortality secondary to recurrences. Dietary supplements like fruits and vegetables are rich in phytochemicals and provide a variety of antioxidants like vitamin A, C, E. Spirulina, Selenium, Green tea (EGCG), Neem, Tomatoes (lycopene), Turmeric (curcumin), and some medicinal mushrooms are also used as chemopreventive and chemotherapeutic agents. This overview emphasizes on natural therapies to fight against oral cancer. Thus, there are several natural compounds that can enhance the prevention of oral cancer.
Keywords: Antioxidants, chemoprevention, chemotherapy, natural micronutrients, oral cancer
|How to cite this article:|
Danaraddi S, Koneru A, Hunasgi S, Ramalu S, Vanishree M. Natural ways to prevent and treat oral cancer. J Oral Res Rev 2014;6:34-9
|How to cite this URL:|
Danaraddi S, Koneru A, Hunasgi S, Ramalu S, Vanishree M. Natural ways to prevent and treat oral cancer. J Oral Res Rev [serial online] 2014 [cited 2020 Jan 27];6:34-9. Available from: http://www.jorr.org/text.asp?2014/6/1/34/140213
| Introduction|| |
Oral cancer is one of the most common and deadliest of diseases all over the world with a five-year survival rate of only 50%. , Annually, an estimated 400,000 people worldwide are newly diagnosed with oral cancer, with the prevalence of oral cancer particularly high among men. According to a study of the World Health Report, published in 2005, the incidence rates for oral cancer vary in men from 1 to 10 cases per a population of 100,000 in many countries. The rate of the oral cancer is 12.6 per a population of 100,000 in India. Males (48.2%) are more affected than females (20.5%). In India 30-35% of the population is affected with oral cancer. 
It has been estimated that 43% of cancer deaths worldwide are due to tobacco with alcohol or areca nut, unhealthy diet, physical inactivity, and infections. Oral carcinogenesis is a multistep process accompanied by genetic changes, which lead to progressive dysplasia, unregulated cell growth, and cancer.
Surgery, radiotherapy, and chemotherapy are the most common treatments designed to stop the spread of oral cancer. Unfortunately during these therapies, many of the body's cells are also damaged or destroyed. In order to reduce the incidence of oral cancer, early diagnosis and prompt treatment of the potentially malignant disorders is necessary. Therefore, natural therapies may be a good substitute.
Dietary supplements like fruits and vegetables, which are rich in phytochemicals, provide a variety of antioxidants like vitamin A, C, E. Spirulina, Selenium, Green tea (EGCG), Neem, Tomatoes (lycopene), Turmeric (curcumin), and some medicinal mushrooms, are also used as chemopreventive and chemotherapeutic agents. ,,, Antioxidants are substances that can inhibit the process of oxidation associated with free radicals. Free radicals are oxidants that are unpaired electrons, which are highly active and are thought to interact with DNA causing cell damage and cancer. 
Antioxidants neutralize free radicals by donating one of their electrons, ending the electron stealing reaction. Furthermore, antioxidant nutrients are stable in either form, and thus, cannot become free radicals by donating an electron. 
In addition, yoga as a way of life, including diet and lifestyle as well as yogasanas, pranayama, and meditation contribute to prevention and long-term remission from cancer.
Mode of action of antioxidants
Antioxidants act through various mechanisms, that is, by inducing apoptosis, an anti-inflammatory, anti-hormonal effect, an immune-enhancing effect, arrest of the cell cycle, and cell differentiation. It also plays a role in gene expression, suppression of proliferation, and angiogenesis, inhibits secondary modification, and development of cancer cells (Dutta et al. 2012; Reddy 2011; Salganik 2001). ,,
Role of antioxidants in oral cancer
Beta-carotene is a vitamin A precursor commonly found in dark green, orange or yellowish fruits and vegetables, such as spinach, carrots, sweet potato, mango, papaya, and oranges.
The main actions of beta-carotene include:
- Antioxidant and free radical scavenging.
- Immunomodulation, stimulation of increase in cell-mediated immune response (T-helper, NK cells, and cells with IL-2 receptors) due to increased monocyte expression and increased activity of tumor necrosis factor alpha.
- Inhibition of mutagenesis.
- Inhibition of cancer cell growth (Shetti et al. 2011; E Siva Prasad Reddy 2011). ,
Beta-carotene is also used for scavenging free radicals such as peroxyl and hydroxyl radicals in areas of low oxygen concentration. In various oral premalignant lesions and conditions, serum beta carotene levels are shown to be decreased and thus its supplementation (30 mg/day) has led to the regression of these lesions. ,,,,
Retinoic acid (vitamin A)
Carotene and animal products such as meat, milk, and eggs are the sources of Retinoic acid. Furthermore, in the intestine, retinoic acid is converted into retinal, and retinol hypervitaminosis occurs when the consumption exceeds the liver's capacity to store retinoids.
The main actions are, it:
- Inhibits keratinization and terminal differentiation of epidermal cells.
- Enhances cellular immunity.
- Arrests/reverses the progression of leukoplakia.
- Induces cytotoxic and cytostatic effects on cancer cells.
- Influences DNA, RNA, and gene expression.
- Interferes with carcinogenic stimulation and binding (Shetti et al. 2011; Reddy 2011; Thriveni et al. 2011). ,,
L-ascorbic acid (vitamin C)
L-ascorbic acid (L-AA), the so-called vitamin C, is found in citrus fruits such as kiwi, strawberries, papaya, and mango. The current US recommended daily allowance for ascorbic acid ranges between 100 and 120 mg/per day for adults. Daily intake of nearly 140 mg/day in case of smokers may typically reduce L-AA concentration in serum leukocytes. L-AA has an antioxidizing property and reacts with the superoxide produced as a result of the cells' normal metabolic processes; this inactivation of superoxide inhibits the formation of nitrosamines during protein digestion and helps avoid damage to the DNA and cellular proteins. L-AA, apart from being an antioxidant, also has the following actions:
- Reduces vitamin E degradation.
- Enhances chemotaxis, phagocytosis, and collagen synthesis.
- Inhibits nitrosamine formation.
- Enhances detoxification via cytochrome p450.
- Blocks formation of fecal mutagens.
- Reduces oncogene expression (Shetti et al. 2011; 2011; Thriveni et al. 2011). ,,
α-tocoferol (vitamin E)
α-tocoferol (AT) is the most common and most active form of vitamin E. It is found in plant oil, margarine, and green leaves. The recommended daily limit rates are 10 mg/day for adult men and 8 mg/day for adult women. α-tocoferol is an effective antioxidant at high levels of oxygen, protecting cellular membranes from lipidic peroxidation.
The main actions of AT include:
- Free radical scavenging.
- Maintenance of membrane integrity, immune function.
- Inhibition of cancer cell growth/differentiation.
- It inhibits mutagenicity and nitrosamine formation.
- Prevents DNA, RNA, and protein synthesis in cancer cells (Shetti et al. 2011; Reddy 2011; Thriveni et al. 2011). ,,
The blue-green microalgae Spirulina, is used in daily diets of natives in Africa and America. Spirulina is the healthiest food containing antioxidants, phytonutrients, essential fatty acids, probiotics, and nutraceuticals. Spirulina is an excellent source of protein, beta-carotene, gamma linolenic acid, B-vitamins, minerals, chlorophyll, sulfolipids, glycolipids, superoxide dismutase, phycocyanin, and enzymes. It is cultivated, processed, and marketed globally for its wealthy dietary products and has been extensively used in health foods, pharmaceutical, and specialty feed sectors. Spirulina has got no side effects and is non-toxic in nature. The nutrients present in Spirulina boost the immune system and enhance the body's ability to generate new blood cells to prevent disease and cancer (Mathew et al. 1995). 
The anticarcinogenic properties of green tea polyphenols - mainly EGCG (epigallocatechin-3-gallate), which is the most biologically active catechin - are likely a result of inhibition of tumor initiation and promotion, induction of apoptosis, and inhibition of cell replication rates, thus retarding the growth and development of neoplasms. The antioxidant potential of green tea polyphenols is directly related to a combination of aromatic rings and hydroxyl groups that make up their structure, and is a result of the binding and neutralization of free radicals by the hydroxyl groups. ,
Epigallocatechin-3-gallate arrest cells in the G 0 -G 1 phase, downregulate cyclin D1, increase p14 ARF and/or p16 protein levels, and thus, stabilize p53 and regulate apoptosis, and block angiogenesis by decreasing the phosphorylation of the vascular endothelial growth factor receptor (VEGF), and inhibit VEGF secretion by tumor cells (Tsao et al. 2009). 
Gallic acid, catechin, and epicatechin are phytochemicals related to oral cancer, which have a carcinogen detoxifying enzyme, glutathione. Catechin can inhibit the production of metalloproteases, reducing the invasion and migration and inducing the apoptosis of cancer cells. It has anti-inflammatory potential by suppressive activation of nuclear factor κ-b (NFκ-b), which induces the apoptosis of cancer cells (Dutta et al. 2012). 
It is one of the most potent antioxidants. Lycopene is a bright red carotene, carotenoid pigment, and a phytochemical found in tomatoes and other red fruits and vegetables, such as, red carrots, watermelons, and papayas. Lycopene has been hypothesized to prevent carcinogenesis and atherogenesis by protecting critical cellular biomolecules, including lipids, lipoproteins, proteins, and DNA. In recent studies, the serum and tissue levels of lycopene have been shown to be inversely associated with the risk of breast cancer, prostate cancer, coronary heart disease and oral premalignant lesions. ,, Lycopene can reduce the risk of oral cancer, as it has been shown to inhibit the proliferation of KB-1 human oral tumor cell by upregulation of connexin-43 (gap junction protein) expressions, concomitant with enhanced gap-junctional communication (Dutta et al. 2012; Livnyet al. 2002). ,
According to various studies, lycopene when given in a dosage of 4-8 mg/day orally for three months leads to a reversal of dysplastic changes in the oral leukoplakia, and 16 mg/day in oral submucous fibrosis. Estimating the daily intake of lycopene has been difficult due to the variability of the reported values in the food sources. On an average, the daily intake of lycopene is estimated to be 3.7 mg (Singh et al. 2004; Kumar et al. 2007). ,
Curcumin is a yellow colored phenolic pigment extracted from turmeric. It is very well-known for its anti-carcinogenic and other therapeutic activity. Curcumin has antitumor activity in the oral cavity, which can also inhibit cell growth and induce apoptosis in oral cancer cells. Curcumin is also associated with downregulation of notch-1, nuclear factor κb (NF-κb), and expression of cyclooxygenase-2 (COX2), liquid oxygen (LOX), iNOS (inducible nitric oxide synthase), matrix metallopeptidase 9 (MMP-9), tumor necrosis factor (TNF), chemokines, and other cell-surface adhesion molecules, and cyclin D1. Curcumin can enhance the cancer-fighting power of the treatment with a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). A recommended daily dose of up to 10 g can suppress tumor initiation, promotion, and metastasis (Dutta et al. 2012; Devasagayam et al. 2004). ,
Mushrooms such as shiitake, maitake, reishi, and some agaricus species fight against cancer and improve the immune system because of the presence of certain glucans and polysaccharide peptides (proteoglycans) (Kidd 2000)  [Figure 1]. Purified bioactive compounds derived from medicinal mushrooms are a potentially new and important source of anticancer agents. Four mushroom samples exhibit excellent mutagenic and anticancer activity.
Selenium (Se) is a trace element having its own codon in the mRNA, selenocysteine (SeCys), which specifies its insertion into the selenoproteins and protects tissues and membranes from oxidative stress and controls the cell redox status. A large SeCys insertion complex formed is machinery for selenoprotein production and has implications for the Se requirements of cancer prevention.
[Table 1] Cellular processes and molecular pathways that may be involved in the anti-cancer effect of selenium (Rayman 2005). 
Selenium forms the active site and increases the inherent levels of antioxidant enzymes in the normal cells, but not in some cancer cells of several antioxidant enzymes, including glutathione peroxidase, which destroys peroxides. A dose of 200 μg/day was found to be associated with significantly enhanced cell-mediated immune responsiveness. Similar to selenium, the minerals manganese and zinc are trace elements that form an essential part of various antioxidant enzymes. ,,,
|Table 1: Cellular processes and molecular pathways that may be involved in the anti-cancer effect of selenium |
Click here to view
Antioxidant enzymes are the enzyme systems that function by catalyzing the oxidation of other molecules. Superoxide dismutase, catalase, and glutathione peroxidase serve as a primary line of defense in destroying free radicals. 
Therapeutic use of antioxidants for oral lesions
The possible uses of antioxidants for oral mucosal lesions include:
- Prevention of lesions in high-risk individuals with mucosa that clinically appear normal, with no history of either premalignant or malignant lesions.
- For treatment of premalignant oral lesions.
- In patients who have had either premalignant or malignant oral lesions that have been successfully treated in order to prevent recurrence of the treated initial lesion or to prevent the development of a second or a separate primary lesion , [Figure 2].
|Figure 2: Antioxidant micronutrients: Protective roles in carcinogenesis|
Click here to view
Thriveni et al. 2011, studied 50 patients with submucous fibrosis, who were divided into two groups. For group A, an intralesional injection of 0.5 ml hyaluronidase 1500 IU and 0.5 ml hydrocortisone acetate 25 mg/ml was injected in the buccal mucosa, bilaterally, in alternative weeks, and a natural beta carotene capsule twice daily was administered for 12 weeks, along with the ice-cream stick mouth exercise. In group B intralesional injections and capsule revox were given twice daily for 12 weeks, along with the ice-cream stick mouth exercise. The study showed statistically significant improvement in mouth opening, reduction in the burning sensation, and decrease in thickness of the collagen bundles in all patients, but with an earlier response in group A than in group B. 
Gowda et al. 2011, studied 12 oral submucous fibrosis patients and evaluated the clinicopathological response to lycopene: A carotenoid antioxidant and improvement was seen after the treatment with lycopene, 2000 µg, twice daily, for three months, with no significant toxicity. 
Yoga as a way of life, including diet and lifestyle as well as yogasanas, pranayama, and meditation contributes tot he prevention and long-term remission from cancer. Yoga has the ability to reverse epigenetic changes against chronic diseases. Yoga treatment may reduce the chances of carcinogenesis. Physical exercise has the ability to kill the emerging cancerous cells naturally. Also performing breathing exercises like pranayama and yoga postures, help individuals in dealing with cancer in a calm manner. Maintaining a healthy immune system is vital to fight the cancerous cells arising in the body, as stress weakens the immune system; yoga and meditation are recommended to alleviate stress [Figure 3].
|Figure 3: Yoga therapies - contribution to cancer prevention and remission[20,21]|
Click here to view
| Conclusion|| |
Antioxidant micronutrients are important not only for limiting oxidative and tissue damage, but also for preventing increased cytokine production, which is a result of the prolonged activation of immune response.
Dietary and other enzymatic antioxidants protect the lipids of lipoprotein and other bio-membranes against oxidative damage by intercepting oxidants before they can attack the tissues. This suggests that antioxidant nutrients can play a significant role in the prevention of oral cancer. It is important to have an adequate antioxidant intake from both diet and supplementation. Hence, let your medicine be your food and your food be your medicine!!!
| References|| |
|1.||Dutta KR, Banerjee S, Mitra A.Medicinal plants of West midnapore, India: Emphasis on phytochemical containment having role on oral cancer. IJP 2012;3:198-208. |
|2.||Yoon AJ, Shen J, Santella RM, Philipone EM, Wu HC, Eisig SB, et al. Topical application of green tea polyphenol (-)-Epigallocatechin-3-gallate (EGCG) for prevention of recurrent oral neoplastic lesions. J Orofac Sci 2012;4:43-50. |
|3.||Shetti N, Patil R. Antioxidants: Its beneficial role against health damaging free radical. World J SciTechnol 2011;1:46-51. |
|4.||Reddy ES. Role of antioxidants in precancerous lesions. JIDA 2011;3:99-101. |
|5.||Seifried HE, McDonald SS, Anderson DE, Greenwald P, Milner JA. The antioxidant conundrum in cancer. Cancer Res 2003;63:4295-8. |
|6.||Salganik RI. The benefits and hazards of antioxidants: Controlling apoptosis and other protective mechanisms in cancer patients and the human population. J Am Coll Nutr 2001;20(Suppl 5):464s-75s. |
|7.||Rhee JC, Khuri FR, Shin DM. Advances in chemoprevention of head and neck cancer. Oncologist 2004;9:302-11. |
|8.||Thriveni R, Praveen AH, Mubeen. Effects of natural beta-carotene and commercially available combination of beta-carotene, vitaminxE, vitamin C and minerals: A prospective comparative study. J Indian Acad Oral Med Radiol 2011;23:554-8. |
|9.||Singh VN, Gaby SK. Premalignant lesions: Role of antioxidant vitamins and beta-carotene in risk reduction and prevention of malignant transformation. Am J Clin Nutr 1991;53(Suppl 1):386s-90s. |
|10.||Mathew B, Sankaranarayanan R, Nair PP, Varghese C, Somanathan T, AmmaBP, et al. Evaluation of chemoprevention of oral cancer with Spirulina fusiformis. Nutr Cancer 1995;24:197-202. |
|11.||Tsao AS,Liu D, Martin J, Tang XM, Lee JJ, El-Naggar AK, et al. Phase II randomized, placebo-controlled trial of green tea extract in patients with high-risk oral premalignant lesions. Cancer Prev Res (Phila) 2009;2:931-41. |
|12.||Gowda BB, Yathish TR, Sinhasan SP, Kumar NH, Purushotham S, Anand D. The response of oral submucous fibrosis to lycopene-A carotenoid antioxidant: A clinicopathological study. J Clin Diagn Res 2011;5:882-8. |
|13.||Livny O, Kaplan I, Reifen R, Polak-Charcon S, Madar Z, Schwartz B. Lycopene inhibits proliferation and enhances gap-junction communication of KB-1 human oral tumor cells. J Nutr 2002;132:3754-9. |
|14.||Singh M, Krishanappa R, Bagewadi A, Keluskar V. Efficacy of oral lycopene in the treatment of oral leukoplakia. Oral Oncol 2004;40:591-6. |
|15.||Kumar A, Bagewadi A, Keluskar V, Singh M. Efficacy of lycopene in the management of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral RadiolEndod 2007;103:207-13. |
|16.||Devasagayam TP, Tilak JC, Boloor KK, Sane KS,Ghaskadbi SS, Lele RD. Free radicals and antioxidants in human health: Current status and future prospects. J Assoc Physicians India2004;52:794-804. |
|17.||Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev 2000;5:4-27. |
|18.||Rayman MP. Selenium in cancer prevention: A review of the evidence and mechanism of action. Proc Nutr Soc 2005;64:527-42. |
|19.||Borek C. Antioxidants and radiation therapy. J Nutr 2004;134:3207S-9S. |
|20.||Available from: http://www.kundalini-and-chakra.com/pranayama.html. [Last accessed on 2013 Jan] |
|21.||Available from: http://www.stherbproducts.com/magazine/yogasanas- [Last accessed on 2013 Jan]. |
[Figure 1], [Figure 2], [Figure 3]
|This article has been cited by|
||Role of lycopene in the prevention of oral precancerous lesions. A review
| ||Shishir Ram Shetty,Sura Ali Ahmed Fuoad Al-Bayati,Mohammed Said Hamed,Hossam Abdelatty Eid Abdemagyd |
| ||The European Research Journal. 2017; |
|[Pubmed] | [DOI]|
||Tumor Preventive Efficacy of Emodin in 7,12-Dimethylbenz[a]Anthracene-Induced Oral Carcinogenesis: a Histopathological and Biochemical Approach
| ||Asokan Manimaran,Shanmugam Manoharan |
| ||Pathology & Oncology Research. 2017; |
|[Pubmed] | [DOI]|
||Chemopreventive Potential of Sunflower Seeds in a Human Colon Cancer Cell Line
| ||Lillian F. Smith,J. Patterson,L.T. Walker,M. Verghese |
| ||International Journal of Cancer Research. 2016; 12(1): 40 |
|[Pubmed] | [DOI]|
||Antioxidant Potential of Coconut Flour in Caco-2 Colon Cancer Cells
| ||Lillian F. Smith,J. Patterson,L.T. Walker,M. Verghese |
| ||International Journal of Cancer Research. 2016; 12(1): 29 |
|[Pubmed] | [DOI]|