CYP1A1 and GSTm expression of hepatocytes induced by 7,12-dimethylbenz(a)anthracene and the influence of ethanolic extract of Gynura procumbens

Iwan Sahrial Hamid, Sugiyanto ., Edy Meiyanto, Sitarina Widyarini

Abstract


The cytochrome P-450 (CYP) and glutathione S-transferase (GST) enzyme systems may influence the biological effects of carcinogens. As such, these enzymes may predict the developmental risk of breast cancer, as well as be potential targets for chemoprevention. The purpose of this study was to compare the expression of CYP1A1 and GST* between treatment groups. Expression of CYP1A1 and GST* was quantified in liver tissue from 18 female Sprague Dawley rats aged 40 days, which randomly divided into six treatment groups. Those are base line group (without DMBA and ethanolic extract treatment), DMBA induced cancer group, the other two groups was administrated by DMBA after treated by ethanolic extract in two different doses, 300 mg /kg BW and 750 mg/kg BW. The last two groups were given two doses of extract ethanolic only, without initiated of DMBA. The ingestion of the extract was carried for three weeks and the ingestion of DMBA was performed twice in the third week. The expression CYP1A1 and GST was quantified by immunohistochemistry. CYP1A1 expression was significantly higher (P < 0.05) in cancer group (DMBA) as compared with other groups. On the other hand, GST expression was lower in cancer group (P < 0.05). Result of this study demonstrated that ethanolic extract leaves of G. procumbens in 300 mg/kg BW dose could inhibit CYP1A1 stronger than are other and induced GST* level. Has effect on ethanolic extract leaves of G. procumbens has ability in played role of as blocking agent in preventing initiation stage of carsinogenesis, therefore it should be taken into account for chemopreventing agent in mammary carsinogenesis.

Key words : Gynura procumbens, breast cancer, Chemopreventive, CYP1A1, GSTμ


References


Anderson, L. E., Boorman, G. A., Morris, J. E., Sasser, L. B., Mann, P. C., Grumbein, S. L., Hailey, J. R., Mc Nally, A., Sills, R. C., and., Haseman, J. K. 1999. Effect of 13 weeks Magnetic Fields Exposure on DMBA-Initiated Mammary Gland Caricinomas in Female Sprague-Dawley Rats, Carcinogenesis, 20 (8), 1615-1620.

Bowman, W. C., and M. J., Rand. 1989, Neoplastic Disease and Anticancer Drugs, in Text Book of Pharmacology, 2nd Ed, Blackwell Scientific Publications, Melbourne, 1- 23.

Ciolino, H. P., Daschner P. J., Wang, T. T., and Yeh, G. C., 1998 . Effect of curcumin on the aryl hydrocarbon receptor and cytochrome P450 1A1 in MCF-7 human breast carcinoma cells. Biochem Pharmacol 56: 197-206.

Harborne, J. B. 1996. The Flavonoids : Advances In Research Since, Chapman and Hall, London.

Hayes, J. D., and Pulford, D. J. 1995. S-Transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprevention and drug resistance. Biochem Mol Biol. 30(6) : 445-600.

Heidel, S. M., Mac Williams, P. S., Baird, W. M., Dashwood, W. M., Buters, J. T. M., Gonzalez, F. J., Larsen, M. C., Czuprynski, C. J., and Jefcoate, C. R., 2000. Cytochrome P4501B1 Mediates Induction of Bone Marrow Cytotoxicity and Preleukemia Cells in Mice Treated wth 7,12-Dimethylbenz[a]anthracene, Cancer Research, 60, 3454-3460.

Heyne, K. 1987. Tanaman Berguna Indonesia, jilid II, cetakan pertama, diterjemahkan oleh Badan Litbang Departemen Kehutanan, Yayasan Sarana Wana Jaya, Jakarta, p. 1029.

Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., and Yamamoto. M., 1999. Keap1 Repress Nuclear Activation of Antioxidant Responsive Elements By Nrf2 Through Binding To The Amino-Terminal Neh2 Domain, Carcinogenesis, 13, (1), 76-86.

Khan, T. H., Jahangir, T., Prasad, L., and Sultana, S. 2006. Inhibitory Effect of Apigenin on Benzo(a)pyrene-mediated Genotoxicity in Swiss Albino Mice, J. Pharm. Pharmacol., 58(12), 1655-1660.

Kubatka, P., Ahlersova E., Ahlers I., Bojkova B., Kalicka K., Adamekova E., Markova M., Chamilova, M. and Cermakova, M., 2002. Variability of Mammary Carsinogenesis Induction in Female Sprague-Dawley and Wista: Han Rats : the Effect of Season and Age, Physiol. Res. , 51,633-640.

Le Blanc., G.A., and W.C., Dauterman. 2001. Conjugation and Elimination of Toxicants, in Hodgson, E., dan Smart, R., C., Introductions to biochemical Toxicology, 3rd ed., A john Wiley & Sons, Inc., New York.

Melendez-Colon,V., Luch,A., Seidel, A., and Baird, W. M., 1999. Cancer Initiation by Polycyclic Aromatic Hydrocarbon Results from Formation of Stable DNA Adducts rather than Apurinic Sites, Carcinogenesis, 20 (10), 1885-1891.

Novalina. 2003. Penggunaan Tanaman Obat Sebagai Upaya Alternatif dalam Terapi Kanker. Pengantar ke Falsafah Sain. PPS Institut Pertanian Bogor.

Nguyen, Sherrat and Pickett. 2003. Transcriptional Regulation of the Rat GSTA2 and NQO1 Genes by Bifunctional and Monofunctional Inducers, Annual Review of Pharmacology and Toxicology, 233-260, diambil dari http://www.eohsi.rutgers.edu, diakses pada Juni 2004.

Ren, W., Qiao, Z., Wang, H., Zhu, L., and Zhang, L., 2003. Flavonoids: Promising Anticancer Agents, Medicinal Research Review, 23 (4): 519-534.

Rizali, E. dan Auerkari Elza, I., 2003. Teknik Pewarnaan Silver (AgNOR) Sebagai Salah Satu Cara Menentukan Aktivitas Proliferasi Sel Tumor dan Apoptosis, Jurnal Kedokteran Gigi Indonesia, 10(3), 41-45.

Rowlands, J. C., Ling He, Hakkak, R., Ronis, M. J. J., and Badger, T. M. 2001, Soy and Whey Proteins Downregulate DMBA-Induced Liver and Mammary Gland CYP1 Expression in Female Rats, Journal of Nutrition, 131, 3281-3287

Russo, M., Tedesco, I., Iacomino, G., Palumbo, R., Galano, G., and Russo, G.L., 2005. Dietary Phytochemicals in Chemoprevention of Cancer, Curr. Med. Chem. – Immun., Endoc. and Metab. Agents, 5, 61-72.




DOI: http://dx.doi.org/10.14499/indonesianjpharm0iss0pp198-206

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