Mode of action of tocotrienol as anticancer

https://doi.org/10.19106/JMedSci005102201909

Widiyasri Lodu(1), Ferry Fredy Karwur(2*)

(1) Graduate Student of Master of Biology Program, Satya Wacana Christian University. Salatiga, Jawa Tengah
(2) Graduate Student of Master of Biology Program, Satya Wacana Christian University. Lecturer Faculty of Medicine and Health Science, Satya Wacana Christian University. Salatiga, Jawa Tengah.
(*) Corresponding Author

Abstract


Tocotrienols are fat soluble substances members of the vitamin E family with the main properties of antioxidant. They are composed of the chiral center of chromanol ring with polypreniyl side chains. Research suggests that tocotrienols have a number of health benefit, and one of them as an anticancer agent. As an anticancer, tocotrienols could perform in different processes of the multi stages of cancer development and interact with other anticancer medicines and other bioactive substances, suchs geneistein, lovastin, hydroxychavicol, 6- gingerol and sesamin. The anticancer activities occur through their roles as antioxidant, coenzyme, gene expression regulator, and preventing cholesterol synthesis by inhibiting the expression of HMGCR enzyme after transcription, through this method, tocotrienols could control the cholesterol level of cancer cells and prevent the growth of the cancer. Tocotrienols target several signalling pathways at cellular and molecular levels.


Keywords


anticancer, antioxidant, bioactive substances, gene expression, HMGCR enzyme, tocotrienol

Full Text:

PDF


References

1. Das S, Lekli I, Das M, Szabo G, Varadi J, Juhasz B, et al.Cardioprotection with palm oil tocotrienols: comparision of different isomers. Am J Physiol Heart Circ 2008; 294(2):970-8.

https://doi.org/10.1152/ajpheart.01200.2007

2. Kasparek S. Chemistry of tocopherols and tocotrienols In: Machlin LJ editor. Vitamin E: a comprehensive treasure. New York: Marcel Dekker Inc., 1980.

3. Bunyan J, McHale D, Green J, Marcinkiewicz S. Biologycal potencies of ε- and ζ1 – tocopherol and 5 – methyltocol. Brit J Nutr 1961; (15):253-57.

https://doi.org/10.1079/BJN19610030

4. Whittle KJ, Dunphy PJ, Pennock JF. The isolation and properties of δ-tocotrienol from hevea latex. Biochem J 1996; 100(1):138-45.

https://doi.org/10.1042/bj1000138

5. Qureshi AA, Burger WC, Peterson DM., Elson CE. The structure of an inhibitor of cholesterol biosynthesis isolated from barley. J Biol Chem 1986; 261(23):10544-50.

6. Guthrie N, Gapor A, Chambers AF, Carroll KK. Inhibition of proliferation of estrogen receptor-negative MDA-MB-435 and positive MCF-7 human breast cancer cell by palm oil tocotrienols and tamoxifen, alone and in combination. J Nut 1997; 127:544S-8S.

https://doi.org/10.1093/jn/127.3.544S

7. Nesaretnam K, Selvaduray KR, Razak GA, Veerasenan SD, Gomez PA. Effectiveness of tocotrienols -rich fraction combined with tamoxifen in the management of women with early breast cancer: a pilot clinical trial. Breast Cancer Res 2010; 12(5):R81.

https://doi.org/10.1186/bcr2726

8. Sundram K, Sambanthamurthi R, Tan Y.A. Palm fruit chemistry and nutrition. Asia Pac J Clin Nutr 2003; 12(3):355–62.

9. Liu D, Shi J, Rodriques L, Sue SJ. Separating Tocotrienols From Palm Oil by Molecular Distillation. Food Rev Int. 2008; (4):376-91.

https://doi.org/10.1080/87559120802303840

10. Frega N,Mozzon M, Bocci F.Identification and estimation of tocotrienolsin the annatto lipid fraction by gas chromatography–mass spectrometry. JAOCS 1998; 75(2):1723-27.

https://doi.org/10.1093/jn/135.2.151

11. Schaffer S, Mϋller WE, Eckert PE. Tocotrienols: constitutional effects in aging and disease. J Nutr 2005; 135(2): 151-4.

12. Knekt P, Reunanen A., Marniemi J, Leino A, Aromaa AA. Low vitamin E status is potential risk factor for insulin dependent diabetes mellitus. J Intern Med 1999; 245(1):99 -102.

https://doi.org/10.1046/j.1365-2796.1999.00416.x

13. Wild S, Roglic G, Green A. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27(5):1047–53.

https://doi.org/10.2337/diacare.27.5.1047

14. Qureshi AA, Salser WA, Palmar Rupar, Emeson EE. Novel tocotrienols of rice bran inhibit atherosclerotic lesions in C57BL/6 ApoE-deficient mice. J Nutr 2001; 131(10):2606-18.

https://doi.org/10.1093/jn/131.10.2606

15. Mayer-Davis EJ, Costacou T, King I. Plasma and dietary vitamin E in relation to incidence of type diabetes: the Insulin Resistance and Atherosclerosis Study (IRAS). Diabetes Care 2002; 25(12):2172–7.

https://doi.org/10.2337/diacare.25.12.2172

16. Nazrun AS, Norazlina M, Norliza M, Nirwana SI. Tocotrienols as an anti-osteoporotic agent: the progress so far. J Osteoporosis Metab Disorders 2011. 4(1):1–14.

https://doi.org/10.3923/ijom.2011.1.14

17. Norazlina M, Ng F W, Ima NirwanaS. γ- tocotrienol is required for normal vitamin D metabolism in female rats. Indian J Pharmaco 2005; 37(5):309-14.

https://doi.org/10.4103/0253-7613.16855

18. Ngah WZ, Jarien Z, San MM, Marzuki A, Top GM, Shamaan NA, et al. Effect of tocotrienol s on hepatocarcinogenesis induced by 2-acetylaminofluorene in rats. Am J Clin Nutr 1990; 53 (4suppl):1076–81.

https://doi.org/10.1093/ajcn/53.4.1076S

19. Nafeeza MI, Kang TT. Synergistic effects of tocopherol, tocotrienol, and ubiquinone in indomethacin-induced experimental gastric lesions. Int J Vitam Nutr Res 2005; 75(2):149–55.

https://doi.org/10.1024/0300-9831.75.2.149

20. Lestariningrum N A, Karwur F F, Martosupono M. Pengaruh vitamin E tokotrienol dan gabungannya dengan asam askorbat terhadap jenis leukosit tikus putih (Rattusnorvegicus L.). Sains Medika 2012; 4(1):46-56.

21. Radhakhrisnan A, Tudawe D, Chakravarthi S, Chiew GS, Haleagrahara N. Effect of γ- tocotrienol in counteracting oxidative and joint in collagen-induced arthritis inrats. Exp Ther Med 2014; 7(5):1408-14.

https://doi.org/10.3892/etm.2014.1592

22. Satymitra M, Ney P, Graves J, Mullaney C, Srinivasan C. Mechanism of radioprotection by d- tocotrienol: pharmacokinetics, pharmacodynamics and modulation of signalling pathways. J Radiol 2012; 85(1019):e1093–e1103.

https://doi.org/10.1259/bjr/63355844

23. Nakagawa K, Shibata A, Yamashita S, Tsuzuki T, Kariya J, Oikawa S, et al. In vivoangiogenesis is suppressed by unsaturated vitamin E, tocotrienol. J Nutr 2007; 137(8): 1938-43.

https://doi.org/10.1093/jn/137.8.1938

24. Shibata A, Nakagawa K, Sookwong P, Tsuduki T,Tomita S, Shirakawa H. Tocotrienol inhibits secretion of angiogenic factors from human colorectal denocarcinoma cells by suppressing hypoxia-inducible factor-1α. J Nutr2008; 138(11):2136-142.

https://doi.org/10.3945/jn.108.093237

25. Hafid SR, Chakravarthi S, Nesaretnam K, Radhakrishnan AK. Tocotrienol adjuvanted dendrit sels inhibit tumor growth and metastasis: a murine model of breast cancer. PLoS One 2013; 19;8(9):e74753.

https://doi.org/10.1371/journal.pone.0074753

26. Lim SW, Loh HS, Ting KN, Bradshaw TD, Zeenathul NA. Cytotoxicity and apoptotic activities of α-, γ- and δ-tocotrienol isomers on human cancer cells. BMC complementary and alternative medicine 2014;14(1):1.

https://doi.org/10.1186/1472-6882-14-469

27. Sylvester PW, Russell M, Ip MM, Ip C. Comparative effects of different animal and vegetable fats fed before and during carcinogen administration on mammary tumorigenesis, sexual maturation and endocrine function in rats. Cancer Res 1986;46(2):757-62.

28. Nesaretnam K, Guthrie N, Chambers AF, Carroll KK. Effect of tocotrienols on the growth of a human breast cancer cell line in culture. Lipids. 1995;30(12):1139-43.

https://doi.org/10.1007/BF02536615

29. Kulkarni S, Ghosh SP, Satyamitra M, Mog S, Hieber K, Romanyukha L, et al. γ-tocotrienol protects hematopoietic stem and progenitor cells in mice after total-body irradiation. Radiation research 2010;173(6):738-47.

https://doi.org/10.1667/RR1824.1

30. Chin SF, Hamid NA, Latiff AA, Zakaria Z, Mazlan M, Yusof YA, et al. Reduction of DNA damage in older healthy adults by Tri E® Tocotrienol supplementation. J Nutr2008;24(1):1-0.

https://doi.org/10.1016/j.nut.2007.08.006

31. Sun W, Wang Q, Chen B, Liu J, Liu H, Xu W. γ-Tocotrienol-induced apoptotic in human gastric cancer SGC-7901 cells is associated with a suppression in mitogen-activated protein kinase signaling. Br J Nutr 2008;99(06):1247-54.

https://doi.org/10.1017/S0007114507879128

32. Punvittayagul C, Sringarm K, Chaiyasut C, Wongpoomchai R. Mutagenicity and antimutagenicity of hydrophilic and lipophilic extracts of Thai Northern purple rice. Asian Pac J Cancer Prev 2013;15:9517-22.

https://doi.org/10.7314/APJCP.2014.15.21.9517

33. Yap WN, Chang PN, Han HY, Lee DT, Ling MT, Wong YC, et al. γ-Tocotrienol suppresses prostate cancer cell proliferation and invasion through multiple-signaling pathways. Br JCancer 2008;99(11):1832-41.

https://doi.org/10.1038/sj.bjc.6604763

34. Srivastava JK, Gupta S. Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptotic selectively in human prostate cancer cells. Biochem Biophys Res Commun 2006; 346(2):447-53.

https://doi.org/10.1016/j.bbrc.2006.05.147

35. Yap WN, Zaiden N, Tan YL, Ngoh CP, Zhang XW, Wong YC, et al. Id1, inhibitor of differentiation, is a key protein mediating anti-tumor responses of γ-tocotrienol in breast cancer cells. Cancer Lett 2010; 291(2):187-99.

https://doi.org/10.1016/j.canlet.2009.10.012

36. Bachawal SV, Wali VB, Sylvester PW. Enhanced antiproliferative and apoptotic response to combined treatment of γ-tocotrienol with erlotinib or gefitinib in mammary tumor cells. BMC Cancer 2010;10(1):1.

https://doi.org/10.1186/1471-2407-10-84

37. Wu SJ & Ng LT. Tocotrienols inhibited growth and induced apoptotic in human HeLa cells through the cell cycle signaling pathway. Integr Cancer Ther 2010;9(1):66-72.

https://doi.org/10.1177/1534735409357757

38. Ye C, Zhao W, Li M, Zhuang J, Yan X, Lu Q, et al. δ-Tocotrienol induces human bladder cancer cell growth arrest, apoptotic and chemosensitization through inhibition of STAT3 pathway. PloS One 2015;10(4):e0122712.

https://doi.org/10.1371/journal.pone.0122712

39. Shah S, Sylvester PW. Tocotrienol-induced caspase-8 activation is unrelated to death receptor apoptotic signaling in neoplastic mammary epithelial cells. Exp Biol Med 2004;229(8):745-55.

https://doi.org/10.1177/153537020422900806

40. Sylvester PW, Akl MR, Malaviya A, Parajuli P, Ananthula S, Tiwari RV, et al. Potential role of tocotrienols in the treatment and prevention of breast cancer. Biofactors 2014;40(1):49-58.

https://doi.org/10.1002/biof.1116

41. Folkman J, Klagsbrun M. Angiogenic factors. Science 1987;235(4787):442-7.

https://doi.org/10.1126/science.2432664

42. King RJB, Robins MW, Cancer biology, 3rd ed. Edinburg: Pearson Education Limited Edinburg Gate Harlow Essex; 2006.

43. Liu HK, Wang Q, Li Y, Sun WG, Liu JR, Yang YM, et al. Inhibitory effects of γ-tocotrienol on invasion and metastasis of human gastric adenocarcinoma SGC-7901 cells.J<span style="font-fa



DOI: https://doi.org/10.19106/JMedSci005102201909

Article Metrics

Abstract views : 1597 | views : 1952


Bookmark and Share


Copyright (c) 2019 Widiyasri Lodu, Ferry Fredy Karwur

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

View My Stats

 

Creative Commons License
Journal of the Medical Sciences (Berkala Ilmu Kedokteran) by  Universitas Gadjah Mada is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Based on a work at http://jurnal.ugm.ac.id/bik/.