BIOACTIVE COMPOUNDS FROM TORBANGUN [Plectranthus amboinicus (Lour.) SPRENG] CHLOROFORM FRACTION INDUCE APOPTOSIS IN BREAST CANCER (MCF-7 CELLS) IN VITRO

https://doi.org/10.22146/tradmedj.24312

Wahid Yulianto(1), Nuri Andarwulan(2*), Puspo Edi Giriwono(3), Joko Pamungkas(4)

(1) Department of Food Science and Technology, Bogor Agricultural University, Bogor Faculty of Animal Husbandry, University of Mataram, Mataram
(2) Department of Food Science and Technology, Bogor Agricultural University, Bogor Southeast Asian Food and Agricultural Science and Technology (SEAFAST) Center, Bogor Agricultural University, Bogor
(3) Department of Food Science and Technology, Bogor Agricultural University, Bogor Southeast Asian Food and Agricultural Science and Technology (SEAFAST) Center, Bogor Agricultural University, Bogor
(4) Department of Animal Disease Science and Veterinary Medicine, Bogor Agricultural University, Bogor Primate Research Center, Bogor Agricultural University, Bogor
(*) Corresponding Author

Abstract


Torbangun (Plectranthus amboinicus (Lour.) Spreng) is a medicinal plant that has been traditionally used in tropical countries to cure various illnesses. The objective of this study was to identify the active compounds in the chloroform fraction which have effect on the apoptosis-related genes expression of breast cancer MCF-7 cells. Apoptosis was observed morphologically using Hoechst nuclear staining. Expression of the genes was analyzed using Real-Time PCR. Chemical compounds of the plant fractions were determined using LC-MS. Result of cell morphology observation clearly indicated apoptosis after the treatment of the plant fraction. Increased expression of anti-apoptotic gene Bcl-2 could not prevent the cells from apoptosis. Expressions of p53 and p21 genes were increased significantly. The expressions of caspase 9, caspase 7 and caspase 1 were increased at concentration-dependent manner. Most of the compounds in the chloroform fraction are identified as diterpenoids which may contribute to the apoptosis inducing activity of the fraction.

Keywords


Apoptosis mechanism; bioactive compounds; chloroform fraction; gene expression; MCF-7 cells; Torbangun

Full Text:

PDF


References

Abbas, T., Dutta, A., 2009. P21 in Cancer: Intricate Networks and Multiple Activities. Nat. Rev. Cancer 9, 400–414. doi:10.1038/nrc2657

Abdel-Mogib, M., Albar, H.A., Batterjee, S.M., 2002. Chemistry of the genus Plectranthus. Molecules. doi:10.3390/70200271

Areche, C., Schmeda-Hirschmann, G., Theoduloz, C., Rodríguez, J. a, 2009. Gastroprotective effect and cytotoxicity of abietane diterpenes from the Chilean Lamiaceae Sphacele chamaedryoides (Balbis) Briq. J. Pharm. Pharmacol. 61, 1689–1697. doi:10.1211/jpp/61.12.0015

Ashkenazi, A., Dixit, V.M., 1998. Death receptors: signaling and modulation. Science 281, 1305–1308. doi:10.1126/science.281.5381.1305

Brandao, E.M., Brandão, P.H.D.M., Souza, I.A., Paiva, G.S., Carvalho, M. de C., Lacerda, C.M., 2013. Antineoplasic Effect of Aqueous Extract of Plectranthus Amboinicus in Ehrlich Ascites Carcinoma. J. Cancer 4, 573–576. doi:10.7150/jca.6730

Burmistrova, O., Simões, M.F., Rijo, P., Quintana, J., Bermejo, J., Estévez, F., 2013. Antiproliferative activity of abietane diterpenoids against human tumor cells. J. Nat. Prod. 76, 1413–1423. doi:10.1021/np400172k

Chin, Y.E., Kitagawa, M., Kuida, K., Flavell, R.A., Fu, X.Y., 1997. Activation of the STAT signaling pathway can cause expression of caspase 1 and apoptosis. Mol. Cell. Biol. 17, 5328–37.

Chipuk, J.E., Maurer, U., Green, D.R., Schuler, M., 2003. Pharmacologic activation of p53 elicits Bax-dependent apoptosis in the absence of transcription. Cancer Cell 4, 371–381. doi:10.1016/S1535-6108(03)00272-1

Chiu, Y.J., Huang, T.H., Chiu, C.S., Lu, T.C., Chen, Y.W., Peng, W.H., Chen, C.Y., 2012. Analgesic and antiinflammatory activities of the aqueous extract from Plectranthus amboinicus (Lour.) Spreng. both in vitro and in vivo. Evidence-based Complement. Altern. Med. 2012. doi:10.1155/2012/508137

Damanik, R., 2009. Torbangun (Coleus amboinicus Lour): a Bataknese traditional cuisine perceived as lactagogue by Bataknese lactating women in Simalungun, North Sumatera, Indonesia. J. Hum. Lact. 25, 64–72. doi:10.1177/0890334408326086

el-Deiry, W.S., 1998. Regulation of p53 downstream genes. Semin. Cancer Biol. 8, 345–57. doi:10.1006/scbi.1998.0097 El-hawary, S.S., El-sofany, R.H., Abdel-Monem, A.R., Ashour, R.S., Sleem, A. a, 2012. Polyphenolics content and biological activity of Plectranthus amboinicus (Lour.) spreng growing in Egypt (Lamiaceae). Pharmacogn. J. 4, 45–54. doi:http://dx.doi.org/10.5530/pj.2012.32.9

Elmore, S., 2007. Apoptosis: a review of programmed cell death. Toxicol. Pathol. 35, 495–516. doi:10.1080/01926230701320337

Gurgel, A.P.A.D., da Silva, J.G., Grangeiro, A.R.S., Oliveira, D.C., Lima, C.M.P., da Silva, A.C.P., Oliveira, R.A.G., Souza, I.A., 2009. In vivo study of the anti-inflammatory and antitumor activities of leaves from Plectranthus amboinicus (Lour.) Spreng (Lamiaceae). J. Ethnopharmacol. 125, 361–363. doi:10.1016/j.jep.2009.07.006

Hasibuan, P.A.Z., 2013. Antioxidant and Cytotoxic Activities of Plectranthus amboinicus (Lour.) Spreng. Extracts. Int. J. Pharm. Teach. Pract. 4, 755–758.

Huang, W.C., Xie, Z., Konaka, H., Sodek, J., Zhau, H.E., Chung, L.W.K., 2005. Human osteocalcin and bone sialoprotein mediating osteomimicry of prostate cancer cells: role of cAMP-dependent protein kinase A signaling pathway. Cancer Res 65, 2303–2313.

Kaliappan, N., Viswanathan, P., 2008. Pharmacognostical studies on the leaves of Plectranthus amboinicus (Lour) Spreng. Int. J. Green Pharm. doi:http://dx.doi.org/10.4103/0973-8258.42740

Livak, K.J., Schmittgen, T.D., 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402–8. doi:10.1006/meth.2001.1262

Lukhoba, C.W., Simmonds, M.S.J., Paton, A.J., 2006. Plectranthus: A review of ethnobotanical uses. J. Ethnopharmacol. doi:10.1016/j.jep.2005.09.011

Marques, C.G., Pedro, M., Simões, M.F.A., Nascimento, M.S.J., Pinto, M.M.M., Rodriguez, B., 2002. Effect of abietane diterpenes from Plectranthus grandidentatus on the growth of human cancer cell lines. Planta Med. 68, 839–840. doi:10.1055/s-2002-34407

Maser, W.H., Yuliana, N.D., Andarwulan, N., 2015. Rapid Identification of Antibacterial Compounds from Turkey Berry by HPLC-Based Metabolomics. J. Liq. Chromatogr. Relat. Technol. 38, 37–41. doi:10.1080/10826076.2015.1032419

Melck, D., Rueda, D., Galve-Roperh, I., De Petrocellis, L., Guzmán, M., Di Marzo, V., 1999. Involvement of the cAMP/protein kinase A pathway and of mitogen-activated protein kinase in the anti-proliferative effects of anandamide in human breast cancer cells. FEBS Lett. 463, 235–240. doi:10.1016/S0014-5793(99)01639-7

Rasikari, H., 2007. Phytochemistry and arthropod bioactivity of Australian Lamiaceae. Southern Cross University. Rzeski, W., Stepulak, A., Szymañski, M., Juszczak, M., Grabarska, A., Sifringer, M., Kaczor, J., Kandefer-Szerszeñ, M., 2009. Betulin Elicits Anti-Cancer Effects in Tumour Primary Cultures and Cell Lines in Vitro. Basic Clin. Pharmacol. Toxicol. 105, 425–432. doi:10.1111/j.1742-7843.2009.00471.x

Simstein, R., Burow, M., Parker, A., Weldon, C., Beckman, B., 2003. Apoptosis, chemoresistance, and breast cancer: insights from the MCF-7 cell model system. Exp. Biol. Med. (Maywood). 228, 995–1003. doi:1535-3702/03/2289-0995

Sprick, M.R., Walczak, H., 2004. The interplay between the Bcl-2 family and death receptor-mediated apoptosis. Biochim. Biophys. Acta - Mol. Cell Res. doi:10.1016/j.bbamcr.2003.11.002

Thirugnanasampandan, R., Ramyaa, G., Gogulramnath, M., Jayakumar, R., Kanthimathi, M.S., 2015. Evaluation of cytotoxic, DNA protecting and LPS induced MMP-9 down regulation activities of Plectranthus amboinicus (Lour) Spreng. essential oil. Pharmacogn. J. 7, 32–36. doi:10.5530/pj.2015.7.3

Visagie, M.H., Birkholtz, L.-M., Joubert, A.M., 2015. A 2-methoxyestradiol bis-sulphamoylated derivative induces apoptosis in breast cell lines. Cell Biosci. 5, 1–15. doi:10.1186/s13578-015-0010-5

Weiss, R.H., 2003. p21Waf1/Cip1 as a therapeutic target in breast and other cancers. Cancer Cell. doi:10.1016/S1535-6108(03)00308-8

Wellsow, J., Grayer, R.J., Veitch, N.C., Kokubun, T., Lelli, R., Kite, G.C., Simmonds, M.S.J., 2006. Insect-antifeedant and antibacterial activity of diterpenoids from species of Plectranthus. Phytochemistry 67, 1818–1825. doi:10.1016/j.phytochem.2006.02.018

Whiteside, G., Cougnon, N., Hunt, S.P., Munglani, R., 1998. An improved method for detection of apoptosis in tissue sections and cell culture, using the TUNEL technique combined with Hoechst stain. Brain Res. Protoc. 2, 160–164. doi:10.1016/S1385-299X(97)00032-9

Yeap, S., Akhtar, M.N., Lim, K.L., Abu, N., Ho, W.Y., Zareen, S., Roohani, K., Ky, H., Tan, S.W., Lajis, N., Alitheen, N.B., 2015. Synthesis of an anthraquinone derivative (DHAQC) and its effect on induction of G2/M arrest and apoptosis in breast cancer MCF-7 cell line. Drug Des. Devel. Ther. 9, 983–992. doi:10.2147/DDDT.S65468

Yulianto, W., Andarwulan, N. Giriwono, P.E., Pamungkas, J., 2016. HPLC-Based Metabolomics to Identify Cytotoxic Compounds from Plectranthus amboinicus (Lour.) Spreng against Human Breast Cancer MCF-7Cells. Journal of Chromatography B. 1039: 28-34. doi:10.1016 /j.jchromb.2016.10.024

Zhang, X., Mukerji, R., Samadi, A.K., Cohen, M.S., 2011. Down-regulation of estrogen receptor-alpha and rearranged during transfection tyrosine kinase is associated with withaferin a-induced apoptosis in MCF-7 breast cancer cells. BMC Complement. Altern. Med. 11, 84. doi:10.1186/1472-6882-11-84.



DOI: https://doi.org/10.22146/tradmedj.24312

Article Metrics

Abstract views : 3386 | views : 2925

Refbacks

  • There are currently no refbacks.


Bookmark and Share


Copyright (c) 2017 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