PHENYLPROPANOIDS, EUGENOL SCAFFOLD, AND ITS DERIVATIVES AS ANTICANCER
Eugenol (EU) is a phenylpropene, an allyl chain-substituted guaiacol. EU is a member of the phenylpropanoids class of chemical compounds. It is a
colorless to pale yellow oily liquid extracted from certain essential oils especially from clove oil. Further, chemopreventive agents might be used singly
or in combination with chemotherapy or radiotherapy for the more effective treatment of cancer by enhancing the efficacy of these modalities with
minimal side effects and toxicity. Considering that EU scaffold may be a prospective chemopreventive agent, its potent antitumor ability to interfere
with solid cancer cell growth and its molecular mechanism were evaluated as an initiative toward the development of a novel strategy for cancer
treatment. This review article will conduct that EU as the antiproliferative activity and molecular mechanism of the EU induced apoptosis against the
cancer cells and animal models.
Keywords: Eugenol, Derivatives of eugenol, Scaffold, Anticancer, Phenylpropanoids.
1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100(1):57-70.
2. Earnshaw WC. Nuclear changes in apoptosis. Curr Opin Cell Biol 1995;7(3):337-43.
3. Vaux DL, Cory S, Adams JM. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 1988;335(6189):440-2.
4. Bonnefoy-Berard N, Aouacheria A, Verschelde C, Quemeneur L, MarÃ§ais A, Marvel J. Control of proliferation by Bcl-2 family members. Biochim Biophys Acta 2004;1644(2-3):159-68.
5. Otake Y, Soundararajan S, Sengupta TK, Kio EA, Smith JC, Pineda-Roman M, et al. Fernandes, overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of Bcl-2 mRNA. Blood 2007;109(7):3069-75.
6. Kelly PN, Strasser A. The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy. Cell Death Differ 2011;18(9):1414-24.
7. Chresta CM, Arriola EL, Hickman JA. Apoptosis and cancer chemotherapy. Behring Inst Mitt 1996;97:232-40.
8. Chao DT, Korsmeyer SJ. BCL-2 family: Regulators of cell death. Annu Rev Immunol 1998;16:395-419.
9. Su YC, Ho CL. Composition, in-vitro anticancer, and antimicrobial activities of the leaf essential oil of Machilus mushaensis from Taiwan. Nat Prod Commun 2013;8(2):273-5.
10. Manjamalai A, Grace VM. The chemotherapeutic effect of essential oil of Plectranthus amboinicus (Lour) on lung metastasis developed by B16F-10 cell line in C57BL/6 mice. Cancer Invest 2013;31(1):74-82.
11. Ashour HM. Antibacterial, antifungal, and anticancer activities of volatile oils and extracts from stems, leaves, and flowers of Eucalyptus sideroxylon and Eucalyptus torquata. Cancer Biol Ther 2008;7(3):399-403.
Asian J Pharm Clin Res, Vol 10, Issue 3, 2017, 41-46
Fadilah et al.
12. Ralph A, Provan GJ. Phytoprotectants. In: Garrow JS, James WP, Ralph A, editors. Human Nutrition and Dietetics. United Kingdom: Elsevier Limited; 2005. p. 417-24.
13. Medina-HolguÃn AL, HolguÃn FO, Micheletto S, Goehle S, Simon JA, Oâ€™Connell MA. Chemotypic variation of essential oils in the medicinal plant, Anemopsis californica. Phytochemistry 2008;69(4):919-27.
14. Shefali A, Shilpi A, Shailey A, Shailey S. Anticancer activities of thiosemicarbazides/thiosemicarbazones: A review. Int J Pharm Pharm Sci 2014;6(9):34-41.
15. Shiny G, Kumaran S, Meena C, Pallavi G, Gururagavan M. Docking studies of novel coumarin derivatives as arylamine N-acetyltransferase 2 inhibitors. Asian J Pharm Clin Res 2012;5(1):94-6.
16. Jaganathan SK, Mazumdar A, Mondhe D, Mandal M. Apoptotic effect of eugenol in human colon cancer cell lines. Cell Biol Int 2011;35(6):607-15.
17. Ghosh R, Nadiminty N, Fitzpatrick JE, Alworth WL, Slaga TJ, Kumar AP. Eugenol causes melanoma growth suppression through inhibition of E2F1 transcriptional activity. J Biol Chem 2005;280(7):5812-9.
18. Jaganathan SK, Mondhe D, Wani ZA, Supriyanto E. Evaluation of selected honey and one of its phenolic constituent eugenol against L1210 lymphoid leukemia. ScientificWorldJournal 2014;2014:912051.
19. Benencia F, CourrÃ¨ges MC. In vitro and in vivo activity of eugenol on human herpesvirus. Phytother Res 2000;14(7):495-500.
20. Chogo JB, Crank G. Chemical composition and biological activity of the Tanzanian plant Ocimum suave. J Nat Prod 1981;44(3):308-11.
21. Asha MK, Prashanth D, Murali B, Padmaja R, Amit A. Anthelmintic activity of essential oil of Ocimum sanctum and eugenol. Fitoterapia 2001;72(6):669-70.
22. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127(12):2893-917.
23. Majeed H, Antoniou J, Fang Z. Apoptotic effects of eugenol-loaded nanoemulsions in human colon and liver cancer cell lines. Asian Pac J Cancer Prev 2014;15(21):9159-64.
24. Park JB, Lee MS, Cha EY, Lee JS, Sul JY, Song IS, et al. Magnolol-induced apoptosis in HCT-116 colon cancer cells is associated with the AMP-activated protein kinase signaling pathway. Biol Pharm Bull 2012;35(9):1614-20.
25. Lin SY, Liu JD, Chang HC, Yeh SD, Lin CH, Lee WS. Magnolol suppresses proliferation of cultured human colon and liver cancer cells by inhibiting DNA synthesis and activating apoptosis. J Cell Biochem 2002;84(3):532-44.
26. Hsu YF, Lee TS, Lin SY, Hsu SP, Juan SH, Hsu YH, et al. Involvement of Ras/Raf-1/ERK actions in the magnolol-induced upregulation of p21 and cell-cycle arrest in colon cancer cells. Mol Carcinog 2007;46(4):275-83.
27. Steven AN, Javaid I, Anthony BM. Why have breast cancer mortality rates declined? J Cancer Policy 2015;5:8-17.
28. Al-Sharif I, Remmal A, Aboussekhra A. Eugenol triggers apoptosis in breast cancer cells through E2F1/survivin down-regulation. BMC Cancer 2013;13:600.
29. Abdel Bar FM, Khanfar MA, Elnagar AY, Badria FA, Zaghloul AM, Ahmad KF, et al. Design and pharmacophore modeling of biaryl methyl eugenol analogs as breast cancer invasion inhibitors. Bioorg Med Chem 2010;18(2):496-507.
30. Baharara J, Ramezani T, Mousavi M, Kouhestanian K. Eugenol suppressed metastasis of breast carcinoma cells and migration by regulation of MMP-9 & paxilin gene expression. Sch J Agric Vet Sci 2015;2(2B):125-30.
31. Vidhya N, Devaraj SN. Induction of apoptosis by eugenol in human breast cancer cells. Indian J Exp Biol 2011;49(11):871-8.
32. Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet 2013;382(9895):889-99.
33. Hemaiswarya S, Doble M. Combination of phenylpropanoids with 5-fluorouracil as anti-cancer agents against human cervical cancer (HeLa) cell line. Phytomedicine 2013;20(2):151-8.
34. Hussain A, Brahmbhatt K, Priyani A, Ahmed M, Rizvi TA, Sharma C. Eugenol enhances the chemotherapeutic potential of gemcitabine and induces anticarcinogenic and anti-inflammatory activity in human cervical cancer cells. Cancer Biother Radiopharm 2011;26(5):519-27.
35. Hussain A, Priyani A, Sadrieh L, Brahmbhatt K, Ahmed M, Sharma C. Concurrent sulforaphane and eugenol induces differential effects on human cervical cancer cells. Integr Cancer Ther 2012;11(2):154-65.
36. Yadav Y, Owens EA, Sharma V, Aneja R, Henary M. Synthesis and evaluation of antiproliferative activity of a novel series of hydroxychavicol analogs. Eur J Med Chem 2014;75:1-10.
37. Bataille V. Genetic epidemiology of melanoma. Eur J Cancer 2003;39(10):1341-7.
38. Chin L. The genetics of malignant melanoma: Lessons from mouse and man. Nat Rev Cancer 2003;3(8):559-70.
39. Arung ET, Matsubara E, Kusuma IW, Sukaton E, Shimizu K, Kondo R. Inhibitory components from the buds of clove (Syzygium aromaticum) on melanin formation in B16 melanoma cells. Fitoterapia 2011;82(2):198-202.
40. Pisano M, Pagnan G, Loi M, Mura ME, Tilocca MG, Palmieri G, et al. Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on malignant melanoma cells. Mol Cancer 2007;6:8.
41. Cam H, Dynlacht BD. Emerging roles for E2F: Beyond the G1/S transition and DNA replication. Cancer Cell 2003;3(4):311-6.
42. Available from: http://www.cancer.org/cancer/leukemia-chronicmyeloidcml/detailedguide/leukemia-chronic-myeloid-myelogenous-key-statistics.
43. Yoo CB, Han KT, Cho KS, Ha J, Park HJ, Nam JH, et al. Eugenol isolated from the essential oil of Eugenia caryophyllata induces a reactive oxygen species-mediated apoptosis in HL-60 human promyelocytic leukemia cells. Cancer Lett 2005;225(1):41-52.
44. Correa P. A human model of gastric carcinogenesis. Cancer Res 1988;48(13):3554-60.
45. Ong CA, Lao-Sirieix P, Fitzgerald RC. Biomarkers in Barrettâ€™s esophagus and esophageal adenocarcinoma: Predictors of progression and prognosis. World J Gastroenterol 2010;16(45):5669-81.
46. Do PM, Varanasi L, Fan S, Li C, Kubacka I, Newman V, et al. Mutant p53 cooperates with ETS2 to promote etoposide resistance. Genes Dev 2012;26(8):830-45.
47. Busuttil RA, Zapparoli GV, Haupt S, Fennell C, Wong SQ, Pang JM, et al. Role of p53 in the progression of gastric cancer. Oncotarget 2014;5(23):12016-26.
48. Sarkar A, Bhattacharjee S, Mandal DP. Induction of apoptosis by eugenol and capsaicin in human gastric cancer AGS cells â€“ Elucidating the role of p53. Asian Pac J Cancer Prev 2015;16(15):6753-9.
49. Manikandan P, Murugan RS, Priyadarsini RV, Vinothini G, Nagini S. Eugenol induces apoptosis and inhibits invasion and angiogenesis in a rat model of gastric carcinogenesis induced by MNNG. Life Sci 2010;86(25-26):936-41.
50. Manikandan P, Vinothini G, Vidya Priyadarsini R, Prathiba D, Nagini S. Eugenol inhibits cell proliferation via NF-kappaB suppression in a rat model of gastric carcinogenesis induced by MNNG. Invest New Drugs 2011;29(1):110-7.
51. Pienta KJ, Smith DC. Advances in prostate cancer chemotherapy: A new era begins. CA Cancer J Clin 2005;55(5):300-18.
52. Ghosh R, Ganapathy M, Alworth WL, Chan DC, Kumar AP. Combination of 2-methoxyestradiol (2-ME2) and eugenol for apoptosis induction synergistically in androgen independent prostate cancer cells. J Steroid Biochem Mol Biol 2009;113(1-2):25-35.
53. Carrasco A, Espinoza C, Cardile V, Gallard OC, Cardona W, Lombardo L, et al. Eugenol and its synthetic analogues inhibit cell growth of human cancer cells. J Braz Chem Soc 2008;19(3):543-8.
54. Prashar A, Locke IC, Evans CS. Cytotoxicity of clove (Syzygium aromaticum) oil and its major components to human skin cells. Cell Prolif 2006;39(4):241-8.
55. Chaieb K, Hajlaoui H, Zmantar T, Kahla-Nakbi AB, Rouabhia M, Mahdouani K, et al. The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzigium aromaticum L. Myrtaceae): A short review. Phytother Res 2007;21(6):501-6.
56. Atsumi T, Fujisawa S, Satoh K, Sakagami H, Iwakura I, Ueha T, et al. Cytotoxicity and radical intensity of eugenol, isoeugenol or related dimers. Anticancer Res 2000;20(4):2519-24.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.