Chemoprevention
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International Journal of Dental and Health Sciences Review Article Volume 05,Issue 01 CHEMOPREVENTION: A REVIEW Amruta M Bansode1,Raghavendra Byakodi2,Avinash Kshar3,Sunil Awale4,Pragati K Kempwade5 1.P.G.Student, Department of Oral Medicine and Radiology, Vasantdada Patil Dental college and hospital ,Sangli, Maharashtra 2.Professor and Guide,Department of Oral Medicine and Radiology,Vasantdada Patil Dental college and hospital,Sangli, Maharashtra. 3.Professor and Head,Department of Oral Medicine and Radiology, Vasantdada Patil Dental college and hospital,Sangli, Maharashtra. 4.Senior Lecturer,Department of Oral Medicine and Radiology,Vasantdada Patil Dental college and hospital,Sangli, Maharashtra. 5.P.G.Student,Department of Oral Medicine and Radiology, Vasantdada Patil Dental college and hospital , Sangli, Maharashtra ABSTRACT: Oral cancer is one of the most common cancers worldwide which is associated with less than 50% of 5 year survival rate. Current treatment modalities available for cancer are surgery, radiotherapy and chemotherapy. These curative therapies affect the quality of life of a patient by affecting speech, swallowing, breathing and also the appearance. Hence preventive modality like chemoprevention can be bought into broader light. Chemoprevention is done with use of natural, synthetic or biologic chemical substances which can prevent, suppress or reverse the process of carcinogenesis. Various chemopreventive agents have been evaluated such as vitamin A, vitamin E, beta carotene and many other dietary products. Newer agents such as cyclooxygenase-2 (COX-2) inhibitors, P53 gene have recently been used and proven effective. This article reviews these chemopreventive agents and their mechanism of action along with aspects of chemoprevention. Key words: oral cancer, chemoprevention, vitamin A & E, COX-2 inhibitors, P53. INTRODUCTION: Cancer is a growing health problem mutagenic damage to DNA, and helps in worldwide, with a steady rise in life prevention of cancer.[3] expectancy. It is a multistage, multi- mechanism carcinogenesis process that It is said “prevention is better than cure” involves mutagenic, cell death and which holds true for oral cancer as the epigenetic mechanisms, during the three therapeutic measures may cause some distinguishable stages: initiation, severe complications; so the promotion, and progression. As reducing chemoprevention will be beneficial in the initiation phase to a zero level is management of oral cancer. impossible, the most effective MECHANISM OF ACTION intervention would be at the promotion phase to eliminate premalignant cells.[1] Mechanisms of cancer chemoprevention is divided into two types: antimutagic Cancer chemoprevention was first and antiproliferative. The mechanism defined in 1976 by Sporn.[2] as a includes induction of cell cycle arrest and pharmacologic modulation of regulatory apoptosis or inhibition of signal pathways, over the effective use of drugs transduction pathways mainly the and micronutrients which block the mitogen-activated protein kinases (MAPK), glycogen synthase kinase (GSK), *Corresponding Author Address: Dr. Amruta M Bansode. E-mail: [email protected] Bansode A..et al, Int J Dent Health Sci 2018; 5(1):99-104 phosphoinositide 3-kinase (PI3K), protein Glucose-6-phosphate dehydrogenase kinases C (PKC) leading abnormal inhibitors cyclooxygenase-2 (COX-2), and nuclear Aspirin factor kappa-light chain-enhancer of 3. Antioxidants activated B cells (NF-kB).[1] COMMONLY TRIED CHEMOPREVENTIVE AGENTS IN ORAL CANCER The rationale of chemoprevention lies in Vitamin A and other retinoids the concept of field carcinogenesis which Beta-carotene was first described in the early 1953 by Vitamin E Slaughter et al. They proposed that Dietary agents carcinogenic exposure of the oral Newer agents mucosa is predisposing factor in the VITAMIN A AND OTHER RETINOIDS development of neoplasm at multiple sites in oral cavity.[2] Vitamin A (retinol) is effective in preventing or suppressing various forms Multifocal areas of cancer develop from of cancer. 13'-cis- retinoic acid induces field carcinogenesis and lateral protective effect in the development of (intraepithelial) spread of genetically secondary cancer in patients with [4] related pre invasive clones. epidermoid cancer of buccal cavity and the pharynx. The protective effects of A recent study by Sharma et al., (2001) retinoids such as retinol, retinal, retinoic shows that several agents, such as acid, and retinal esters on AFB nonsteroidal anti-inflammatory drugs carcinogenicity are due to inhibition of (NSAIDs), retinoids and SERMS have AFB1-DNA adduct formation resulting in antiangiogenic activity.[5] less epoxide formation by affecting IV.CLASSIFICATION OF CYP450 systems.[7] CHEMOPREVENTIVE AGENTS Vitamin A induces the activity of Pharmacological and chemical structural glutathione S-transferase and enhances classification of chemopreventive the detoxification of AFB1-epoxide. agents.[6] Retinoids have been used as 1.Antimutagens/carcinogen blocking chemopreventive agents in potentially agents malignant disorders like leukoplakia Phase II metabolic enzyme inducers which usually develops in an invasive N-acetyl-L-cysteine squamous cell carcinoma. Polyphenols Retinoids also show transactivation Curcumin, dehydroepiandrosterone activity, suppressing activity of other (DHEA) transcription factors, such as AP-1, which 2. Antiproliferatives are critical mediators of transrepression Retinoids/Carotenoids: β-carotene, 13- activity. Retinoid transrepression activity cis-retinoic acid, vitamin A. 100 Bansode A..et al, Int J Dent Health Sci 2018; 5(1):99-104 is linked to retinoid antiproliferative Vitamin E and menadione (a water- activity and also transactivation activity soluble synthetic vitamin K) prevent AFB1 is linked to induction of differentiation. -induced mutagenesis in the Ames bacterial system.[7] BETA CAROTENE Vitamin E inhibits cancer development In the late 1970s beta-carotene was via various mechanisms such as down discovered as a possible anticancer regulation of p53, stimulation of wild agent. Beta-carotene is known as a type of p53, blockage of transforming carotenoid, which apparentely acts as an GF-ɑ causing anti-angiogenic effect, antioxidant and has cancer protective activation of heat shock proteins. ability. DIETARY AGENTS It is one of the most efficient substances that quenches the excitation energy of Routine consumption of fruits and singlet oxygen and traps organic free vegetables is strongly associated with radicals.[8] The Beta-Carotene and Retinol reduced risk for many of the cancers. Efficacy Trial (CARET) is one of several The strongest evidence pertains to recent trials conducted to assess the reduced risk for cancers of the mouth chemopreventive efficacy and safety of and pharynx, esophagus, stomach and beta carotene and related agents.[9] Beta lungs.[10] carotene has been proven to be more effective in initiation phase than in The NCI has identified about 35 plant- promotional phase. It has an inhibitory based foods that possess cancer- action on lipid peroxidation in chemically preventive properties such as garlic, induced neoplastic transformation. soybeans, turmeric, tomatoes and cruciferous vegetables (for example, Advantage of carotenoids is that they are broccoli, cauliflower and Brussels nontoxic relatively with most common sprouts).[11] complication being yellow discoloration of skin. The recent search for anticarcinogenic substances in fruits and vegetables VITAMIN E includes identification of anti inflammatory compounds which The term vitamin E describes a family of influence the generation of light antioxidants. Alpha-tocopherol is prostaglandins.[10] the only form of vitamin E which is actively maintained in human body LYCOPENE .Vitamin E (alpha-tocopherol) is a potent antioxidant; neutralizes free oxygen Lycopene is a phytochemical, radicals and inhibits formation of synthesized by plants and carcinogenic nitrosamine. microorganisms. It is not synthesized by 101 Bansode A..et al, Int J Dent Health Sci 2018; 5(1):99-104 animals.It is an acyclic isomer of beta- that capsaicin is a carcinogen or tumor carotene.[12] Lycopene, gives the ripe promoter, others have reported that it tomato its bright red color and is a very has chemopreventive effects. effective natural antioxidant, quencher Interestingly, capsaicin has been found of free radicals and DNA protector.[13] to preferentially repress the growth of Lycopene's bioprotective activity enables some transformed human cells.[15] it to inactivate free radicals.[12] It protects Capsaicin inhibits constitutive and DNA from the damage induced by 1- induces activation of NF-kB in human methyl-3-nitro-1-nitrosoguanideand malignant melanoma cells and causes [13] H2O2. Lycopene suppresses oral inhibition of melanoma cell carcinogenesis induced by DMBA. proliferation.[11] Though it is known as an antioxidant, in bioprotective activity both oxidative and RESVERATROL non oxidative mechanisms are involved. Resveratrol (3,4′,5-trihydroxy- CURCUMIN transstilbene) is a phytoalexin present in grapes. It is an antioxidant ingredient of Curcumin a yellow pigment present in red wine. Resveratrol causes dose- the rhizome of turmeric (Curcuma longa dependent inhibition of recombinant L). It is species is one of the most human COX-2 enzyme activity, inhibits extensively investigated phytochemicals, the redistribution of PKC activity induced and has chemopreventive potential. by PMA, inhibits PMA-mediated Topical application of curcumin