20May 2018

CHEMOPREVENTION OF LUNG CARCINOGENESIS IN STRAIN BALB/C MICE WITH POLYPHENOLS OF MAHKOTA DEWA (Phaleria macrocarpa) FROM INDONESIAN HERBAL.

Crossref Cited-by Linking logo
  • Abstract
  • Keywords
  • References
  • Cite This Article as
  • Corresponding Author

Backgroud and objective: Polyphenols of Mahkota Dewa (Phaleria macrocarpa) has potential as anticancer that is expected to inhibit lung carcinogenesis, but it has not been widely studied. This study aims to prove the role of Mahkota Dewa polyphenols to inhibit the progression of lung carcinogenesis development in mice. Methods: The design used in this study is posttest serial control group design with 40 strain Balb/c mice as samples, aged 1-2 weeks, weighted 20-30 g, and in healthy condition. All mice were induced using B(a)P then were randomized into 2 groups: the control group and the 50 mg polyphenols treatment group. The development of lung tumor was observed with tissue surgery at week-8, -17, and -26. The examination of lung carcinogenesis incidence was done using H&E staining. Results: The data were analyzed using Kruskal-Wallis, Mann-Whitney, with significance level of p<α (0.05). Oral administration of Mahkota Dewa?s polyphenols significantly showed the inhibition of lung carcinogenesis incidence in the treatment group at week-8, -17, and -26 (p=0.000). The incidence of lung carcinogenesis in the control group at week-8, -17, and -26 were 2.32?0.26 and 3.93?0.46; while in the treatment group were 1.88?0.38 and 0.88?0.22 (p=0,000). Conclusion: The administration of Mahkota Dewa?s polyphenols was effective to inhibit lung carcinogenesis in Balb/c strain mice.


  1. Archivio MD?, Santangelo C, Scazzocchio B, Vari R, Filesi C, Masella R, Giovannini C. Modulatory effects of polyphenols on apoptosis induction: relevance for cancer prevention. Int. J. Mol. Sci. 2008; 9: 213-228.
  2. Banerjee S, Manna S, Mukherjee S, Pal Debalina, Panda CKr, Das S. Black tea polyphenols restrict benzo(a)pyrene-induced mouse lung cancer progression through inhibition of Cox-2 and induction of caspase-3 expression. Asian Pacific J Cancer Prev 2006a; 7: 661-666.
  3. Banerjee S, Manna S, Saha P, Panda CKr, Das S. Black tea polyphenols suppress cell proliferation and induce apoptosis during benzo(a)pyrene-induced lung carsinogenesis. European Journal of Cancer Prevention, 2005; 14: 215-221.
  4. Banerjee S, Panda CKr, Das S. Clove, a potential chemopreventive agent for lung cancer. Carcinogenesis 2006b; 27(8): 1654-1654.
  5. Bonner A. E, Lemon W. J, Devereux T. R, Lubet R. A, You M. Molecular profiling of mouse lung tumors: association with tumor progression, lung development and human lung adenocarcinoma. Oncogene 2004; 23: 1166-76.
  6. Caputi M, Russo G, Esposito V, Mancini A, Giordano A. Role of cell-cycle regulators in lung cancer. Journal of Cellular Physiology 2005; 205: 319-327.
  7. Duarte RL de M, Paschoal MEM. Molecular markers in lung cancer: prognosis role and relationship to smoking. J. Bras. Pneumol. 2005; 32(1): 56-65.
  8. Esposito V, Groeger AM, De Luca L, Di Marino M, Santini D, Marchei P, Baldi F, Wolner E, Baldi A. 2002. Expression of surface protein receptors in lung cancer. Anticancer Res 22(6C):4039? 4043.
  9. Estensen RD, Jordan MM, Wiedmann, Galbraith AR, Steele VE, Wattenberg. Effect of chemopreventif agents on separate stages of progression of benzo(a)pyrene induced lung tumors in A/J mice. Carcinogenesis 2004; 25(2): 197-201.
  10. Fisher DE. Apoptosis in the cancer therapy: crossing the threshold. Cell 2004; 78: 539-542.
  11. Frei B and Higdon J. V. Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. Journal of Nutrition 2003; 133: 3275S-3284S.
  12. Giovannini C, Scazzocchio B, Vari R, Santangelo C, Archivio D? M and Masella R. Apoptosis in cancer and artherosclerosis: poliphenol activities. Ann Ist Suoer Sabita 2007; 43(4): 406-416.
  13. Goldfarb R, Mineo TC, Baldi A, Wolner E. 2004. Prognostic value of Groeger AM, Caputi M, Esposito V, Baldi A, Rossiello R, Santini D, Mancini A, Groeger AM, Caputi M, Esposito V, Baldi A, Rossiello R, Santini D, Mancini A, Kaiser HE, Baldi F. 2000. Expression of p21 in non-small cell lung cancer relationship with PCNA. Anticancer Res 20(5A):3301? 3305.
  14. Groeger AM, Caputi M, Esposito V, Baldi A, Rossiello R, Santini D, Mancini A, Kaiser HE, Baldi F. 2000. Expression of p21 in non-small cell lung cancer relationship with PCNA. Anticancer Res 20(5A):3301? 3305.
  15. Groeger AM, Esposito V, De Luca A, Cassandro R, Tonini G, Ambrogi V, Baldi F, Goldfarb R, Mineo TC, Baldi A, Wolner E. 2004. Prognostic value of immunohistochemical expression of p53, bax, Bcl-2 and Bcl-xL in resectednon-small-cell lung cancers. Histopathology 44(1):54? 63.
  16. Kassie F, Matise I, Negia M, Upadhyaya P, Hecht SS. Dose-dependent inhibition of tobacco smoke carcinogen?induced lung tumorigenesis in A/J mice by indole-3-carbinol. Cancer Prev. Res. 2008; 1(7): 568-576.
  17. Kuo PL, Lin CC. Green tea constituent (-)-epigallocatechin-3-gallate inhibits Hep G2 cell proliferation and induces apoptosis through p53-dependent and Fas-mediated pathways. J Biomed Sci 2003; 10: 219-27.
  18. Lee HJ, Wang CJ, Kuo HC, Chou FP, Jean LF, Tseng TH. Induction apoptosis of luteolin in human hepatoma HepG2 cells involving mitochondria translocation of Bax/Bak and activation of JNK. Toxicol Appl Pharmacol 2005; 203: 124-31.
  19. Malkinson AK. Primary lung tumors in mice as an aid for understanding, preventing, and treating human adenocarcinoma of the lung. Lung Cancer 2001; 32: 265-79.
  20. Manson M. Cancer prevention- the potential for diet to modulate molecular signaling. Trends Mol Med. 2003; 9:11-18.
  21. Michael G, Watjen W, Niering P, Steffan B, Thi QH, Chovolou Y, Kampkotter A, Bast A, Proksch P, Kahl R. Pro-apoptosis effects of the flavonoid luteolin in rat H4IIE cells. Toxicology 2005; 206: 337-48.
  22. Minna JD, Roth JA, Gazdar AF. Focus on lung cancer (review). Cancer Cell 2002; 1:49?52.
  23. Murwanti R, Meiyanto E, Nurrochmad A and Kristina SA, 2004. Efek ekstrak etanol rimpang temu putih (Curcuma zedoria ) terhadap pertumbuhan tumor paru fase post inisiasi pada mencit betina diinduksi benzo(a)piren. Majalah Farmasi Indonesia, 15(1):7-12.
  24. Ong CS, Tran E, Nguyen TT, Ong CK, Lee SK, Lee JJ, Ng CP, Leong C, Huynh H. Quercetin-induced growth inhibition and cell death in nasopharyngeal carcinoma cells are associated with increase in Bad and hypophosphorylated retinoblastoma expressions. Oncol Rep 2004; 11: 727-33.
  25. Porrini M, Riso P, Brusamolino A, Berti C, Guarnieri S, Visioli F. Daily intake of a formulated tomato drink affects carotenoid plasma and lymphocyte concentrations and improves cellular antioxidant protection. Br J. Nutr. 2005; 93: 93-99.
  26. Rahman I, Yang SR, Biwas SK, 2006. Current concepts of redox signaling in the lungs. Antioxid Redox Signal 8:681-9.
  27. Rice-Evans CA, Miller NJ, Bolwell PG, Bramley PM, Pridham JB. The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radic Res 2005; 22: 375-83.
  28. Sang SM, Lee MJ, Hou Z, 2005. Stability of tea polyphenol (-)-epigallocatechin-3-gallate and formation of dimers and epimers under common experimental conditions. J Agric Food Chem, 53: 9478-9484.
  29. Selvendiran K, Koga H, Ueno T, Yoshida T, Maeyama M, Torimura T, Yano H, Kojiro M, Sata M. Luteolin promotes degradation in signal transducer and activator of transcription 3 in human hepatoma cells: an implication for the antitumor potential of flavonoids. Cancer Res 2006; 66: 4826-34.
  30. Shimizu M, Deguchi A, Lim JT, Moriwaki H, Kopelovich L, Weinstein IB. (-)-Epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells. Clin Cancer Res 2005; 11: 2735-46.
  31. Soeksmanto A. Pengaruh ekstrak butanol buah tua mahkota dewa (Phaleria macrocarpa [Scheff.] Boerl.) terhadap jaringan ginjal mencit (Mus musculus). Biodiversitas 2006a; 7(3): 278-281.
  32. Soeksmanto A. Pengaruh ekstrak butanol buah tua mahkota dewa (Phaleria macrocarpa [Scheff.] Boerl.) terhadap jaringan hati mencit (Mus musculus). Biodiversitas 2006b; 7(4): 340-343.
  33. Sun S-Y, Numsen Hail Jr, Reuben Lotan. Apoptosis as a Novel Target for Cancer Chemoprevention. Journal of the National Cancer Institute 2004; 96(9) 662-672.
  34. Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 2003; 3:768-780.
  35. Thomasset SC, Berry DP, Garcea G, Marczylo T, Steward WP and Gescher AJ, 2007. Dietary polyphenolic phytochemicals-promising cancer chemopreventive agents in humans? A review of their clinical properties. Int J Cancer 120: 451-458.
  36. Wang ZY, Huang MT, Lou YR, Xie JG, Reuhl KR, Newmark HL, Ho CT, Yang CS, Conney AH. Inhibitory effects of black tea, green tea, decaffeinated black tea and decaffeinated green tea on ultraviolet B light-induced skin carcinogenesis in 7,12-dimethylbenz(a)anthracene-initiated SKH-1 mice. Cancer Res. 19945; 4: 3428-3435.
  37. Wattenberg LW, Wiedmann TS, Estensen RD, Zimmerman CL, Galbraith AR, Steele VE, Kelloff GJ. Chemoprevention of pulmonary carcinogenesis by brief exposures to aerosolized budesonide or beclomethasone diproprionate and by the combination of aerosolized budesonide and dietary myo-inositol. Carcinogenesis 2000; 21: 179-182.
  38. Widyasari A, Riastiti Y, Astuti l, Susilowati R, Harijadi. Efek biji mahkota dewa terhadap ekspresi caspase-3 aktif pada ce1 line Ca colon WiDr. Berkala llmu Kedokteran 2006; 38 (1): 24-29.
  39. Yang CS, Wang X, Lu G, and Picinich SC, 2009. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer: 9(6): 429?439.
  40. Yang CS, Wang ZY. Tea and cancer; a review. J Natl Cancer Inst 1993; 85: 1038-49.
  41. Yang G, Wang ZY, Kim S, Liao J, Seril DN, Chen X, Smith TJ, Yang CS. Characterization of early pulmonary hyperproliferation and tumor progression and their inhibition by black tea in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model with A/J mice. Cancer Res. 1997; 57: 1889-94.
  42. Yao LH, Jiang YM, Shi J, Tomas-Barberan FA, Datta N, Singanungsong R, Chen SS. Flavonoids I food and their health benefits. Plant Foods Hum. Nutr. 2004: 59: 113-22.
  43. Zhai S, Dai R, Friedman F, Vestal R. Comparative inhibition of human cytochromes p450 1A1 and 1A2 by flavonoids. Drug Metabolism and Disposition 2008; 26: 989-992.
  44. Zochbauer-Muller S, Gazdar AF, Minna JD. Molecular pathogenesis of lung cancer. Annu Rev Physiol 2002; 64: 681-708.

[Theopilus Wilhelmus Watuguly. (2018); CHEMOPREVENTION OF LUNG CARCINOGENESIS IN STRAIN BALB/C MICE WITH POLYPHENOLS OF MAHKOTA DEWA (Phaleria macrocarpa) FROM INDONESIAN HERBAL. Int. J. of Adv. Res. 6 (May). 580-590] (ISSN 2320-5407). www.journalijar.com


Theopilus Wilhelmus Watuguly
General Biology Laboratory and Biomedical Research University of Pattimura Ambon

DOI:


Article DOI: 10.21474/IJAR01/7069      
DOI URL: http://dx.doi.org/10.21474/IJAR01/7069