POTENCY OF CITRUS PEELS (Citrus aurantiifolia (Cristm.) Swingle) ETHANOLIC EXTRACT AS CHEMOPREVENTIVE AGENT THROUGH DOWNREGULATION OF c-Myc EXPRESSION AND INHIBITION OF 7.12-DIMETHYLBENZ[a]ANTRACHENE INDUCED FEMALE SPRAGUE DAWLEY RATS BREAST CELL PROLIFERATION

https://doi.org/10.22146/tradmedj.8063

Dewi Pratiwi(1), Novi Hastuti(2), Niken Nur W(3), Inna Armandari(4), Muthi’ Ikawati(5), Adam Hermawan(6), Edy Meiyanto(7*)

(1) Faculty of Pharmacy, Universitas Gadjah Mada
(2) Faculty of Pharmacy, Universitas Gadjah Mada
(3) Faculty of Pharmacy, Universitas Gadjah Mada
(4) Faculty of Pharmacy, Universitas Gadjah Mada
(5) Faculty of Pharmacy, Universitas Gadjah Mada
(6) Faculty of Pharmacy, Universitas Gadjah Mada
(7) Faculty of Pharmacy, Universitas Gadjah Mada
(*) Corresponding Author

Abstract


The using of natural-based medicine is growing rapidly in societies. Besides being cheap and affordable, natural-based medicine is relatively safer than the synthetic drugs. Peel of Citrus aurantifolia (Cristm.) Swingle) is one of the chemopreventive agent which contain flavonoids have potency as anticarcinogenic agent. This study is designed to study the potency of Citrus aurantifolia peel ethanolic extract in proliferation inhibition of Rattus norvegicus mammary cell of Sprague Dawley strain which is induced by 7,12-Dimethylbenz[a]anthracene (DMBA). Rats were divided into five groups consist of DMBA treatment, CMC-Na treatment, extract 1500 mg/kgBW treatment, treatment of DMBA+ extract 750 mg/kgBW and DMBA+ extract 1500 mg/kgBW. At the beginning of the tenth week of the study, breasts was isolated and stored in 10% formalin buffer. Observation of cell proliferation was done by AgNOR method. C-Myc expression observed using immunohistochemistry (IHC). Observation of mammary cell with AgNOR method indicated that the treatment of Citrus aurantifolia peel ethanolic extract can inhibit cell proliferation significantly. Dosage 1500 mg/kgBW gave higher inhibition effect than dosage 750 mg/kgBW. IHC result showed that treatment of Citrus aurantifolia peel ethanolic extract decrease the expression of c-Myc. Dosage 750 mg/kgBW gave lower decreasing effect than dosage 1500 mg/kgBW. Citrus aurantifolia peel ethanolic extract inhibited the proliferation of mammary cell induced DMBA through the inhibition of c-Myc expression in dose dependent phenomena so that it is a potential chemopreventive agent.


Keywords


proliferation; Citrus aurantiifolia; AgNOR; Immunohistochemistry; c-myc



References

Basu, G, D., Pathangey, L.B., Tinder, T.L., Gendler, S.J., and Mukherjee, P. (2004). ‘Mechanisms Underlying the Growth Inhibitory Effects of the Cyclo-Oxygenase-2 Inhibitor Celecoxib in Human Breast Cancer Cells’, J. from Breast Cancer Research, 2(11), 632-642

Choi, Soo-Youn., Ko, Hee-Chul., Ko, Soo-Youn., Hwang, Joon-Ho., Park, Ji-Gweon., Kang, Shin-Hae., Han, Sang-Hun., Yun, Su-Hyun., and Kim, Se-Jae. (2007). ‘Correlation between Flavonoid Content and the NO Production Inhibitory Activity of Peel Extracts from Various Citrus Fruits’, Biol. Pharm. Bull. 30(4) 772-778

De Leo, F. and Del Bosco, F.S. (2005). Citrus Flavonoids as Bioactive Compounds: Role, Bioavailability, Socio-Economic Impact and Biotechnological Approach For Their Modification, 9th ICABR International Conference on Agricultural Biotechnology: Ten Years Later, Ravello, Italy

Hertog MGL, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S, Pekkarinen M, Simic BS, Toshima H, Feskens E, Hollman PCH and Katan MB (1995) Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 155:381–386

Morley, Karen, Ferguson, Peter., and Korotpatnick, J., 2007, Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human breast and colon cancer cells, Cancer Letters, 251(1), 168-178

Scambia G, Ranelletti FO, Panici PB, Piantelli M, Rumi C, Battaglia F, Larocca LM, Capelli A and Mancuso S (1990b) Type-II estrogen binding sites in a lymphoblastoid cell line and growth-inhibitory effect of estrogen, anti-estrogen and bioflavonoids. Int J Cancer 46:1112–1116

Shiu, Robert P., Watson, Peter H., and Dubik, Don, 1993, c-myc Oncogene Expression in Estrogen-Dependent and -Independent BreastCancer, Clin. Chem. 39/2, 353-355

Singletary, K., MacDonald, C., and Wallig, M., 1997, The plasticizer benzyl butyl phthalate (BBP) inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary DNA adduct formation and tumorigenesis, Carcinogenesis, 18(8),1669–1673

Vanamala, J., Leonardi , Tety., Patil, Bhimanagouda S., Tadde, Stella S., Murphy, Mary E., Pike, Leonard M., Chapkin, Robert S., Lupton, Joanne R., and Turner, and Nancy D. (2005). ‘Suppression of colon carcinogenesis by bioactive compounds in grapefruit’, Carcinogenesis Advance Access. Oxford University press, England

Zhang, C., Lu, Y., Tao, L., Su, X., andWei, D. (2007). ‘Tyrosinase inhibitory effects and inhibition mechanisms of nobiletin and hesperidin from citrus peel crude extracts’, J. Enzyme Inhib Med Chem. 22(1):91-8



DOI: https://doi.org/10.22146/tradmedj.8063

Article Metrics

Abstract views : 1310 | views : 9920

Refbacks

  • There are currently no refbacks.




Copyright (c) 2010 Majalah Obat Tradisional

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

©Majalah Obat Tradisional (Traditional Medicine Journal)
 ISSN 2406-9086
Faculty of Pharmacy
Universitas Gadjah Mada