Paper ID:505

Propolis and Mangostin Inhibit Mammary Gland Cancer Development in Female Mice Balb/C

Marselina Irasonia Tan & Irham Hayati
School of Life Sciences and Technology,
Institut Teknologi Bandung, Jl. Ganesha 10, Bandung 40132, IndonesiaEmail:

Received June 19th, 2014, Revised September 28th, 2016, Accepted for publication December 20th, 2016

Abstract. Breast cancer development involves many processes, including angiogenesis and metastasis. Many factors play an important role in angiogenesis such as HIF-1α and in metastasis, i.e. FAK and Wnt2. The aim of this study was to observe the effect of propolis and mangostin on mammary gland cancer development and on the expression of wnt2 and FAK in Balb/C mice. Mammary gland tumor development in Balb/C mice was induced by DMBA. Mice were divided into 5 groups of treatment: negative control (K-); positive control (Dx) which were treated with doxorubicin (14.04 mg/kg b.w.); mice treated with Propolis (0.32 mg/kg bw) (P) or mangostin (0.128 mg/kg b.w.) (M) or combination of Propolis (0.32 mg/kg b.w.) and mangostin (0.128 mg/kg b.w.) (MP). Both Mangostin and propolis did not affect mice body weight. Treatment with propolis or treatment with propolis combined with mangostin was able to reduce tumor development activity in Balb/C mice. Moreover, combination of Mangostin and propolis is able to lower Wnt2, FAK and HIF-1α expression.  It can be concluded that combination of propolis and mangostin is potential to inhibit cancer development through downregulation of Wnt2, FAK, and HIF1α expression.

Keywords: angiogenesis; mammary cancer; mangostin; metastasis; propolis.



Ferlay, J., Shin, H.R., Bray, F., Forman, D., Mathers, C., & Parkin, D.M., Estimates of Worldwide Burden of Cancer in 2008: GLOBOCAN 2008,  Int. J. Cancer, 127(12), pp. 2893–2917, 2010.

Pugh, C.W. & Ratcliffe, P.J., Regulation of Angiogenesis by Hypoxia: Role of the HIF System, Nat. Med., 9(6), pp. 677-684, 2003.

Zhao, J. & Guan, J.L., Signal Transduction by Focal Adhesion Kinase in Cancer, Cancer Metastasis Rev., 28(1-2), pp.35-49, 2009.

Witze, E.S., Litman, E.S., Argast, G.M., Moon, R.T., & Ahn, N.G., Wnt5a Control of Cell Polarity and Directional Movement by Polarized Redistribution of Adhesion Receptors, Science, 320 (5874), pp. 365–369, 2008.

Park, S.I., Ohta, T., Kumazawa, S., Jun, M.,  & Ahn, M.R., Korean Propolis Suppresses Angiogenesis through Inhibition of Tube Formation and Endothelial Cell Proliferation, Nat. Prod. Commun., 9(4), pp.555-560, 2014

Izuta, H., Tsuruma, K., Araki, Y., Mishima, S., & Hara, H., Bee Products Prevent VEGF-Induced Angiogenesis in Human Umbilical Vein Endothelial Cells, B.M.C. Complement Altern. Med. 9(45), 2009.

Syamsudin, P.S., Djamil, R., & Heffen, W.L., Apoptosis of Human Breast Cancer Cells Induced- by Ethylacetate Extracts of Propolis, American J. Biochem. Biotech., 6(2), pp. 84-88, 2010.

Matsumoto, K., Akao. Y., Kobayashi, E., Ohguchi, K., Ito, T., Tanaka, T., Iinuma, M., & Nozawa, Y., Induction of Apoptosis by Xanthones from Mangosteen In Human Leukemia Cell Lines, J. Nat. Prod., 66(8), pp.1124-1127, 2003.

Tan, M.I. & Sophianie, B.N.E., Effects of Mangostin on the Activity of  Protein Kinase A and Expression of Estrogen Receptor in Human Breast Cancer Cell Line, International Conference on Advances in Biotechnology and Pharmaceutical Sciences (ICABPS'2011), Bangkok: pp. 238-242, 2011.

Umthong, S., Phuwapraisirisan, P., Puthong, S., & Chanchao, C., In Vitro Antiproliferative Activity of Partiallypurified Trigona Laeviceps Propolis from Thailand on Human Cancer Cell Lines, B.M.C. Complement Altern. Med., 11(37), 2011.

Sugimoto, Y., Iba, Y., Kayasuga, R., Kirino, Y., Nishiga, M., Hossen, M.A., Okihara, K., Sugimoto, H., Yamada, H., & Kamei, C., Inhibitory Effects of Propolis Granular A.P.C. on 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone-Induced Lung Tumorigenesis in A/J Mice, Cancer Let.,193, pp.155–159, 2003.

Kosem, N., Ichikawa, K., Utsumi, H., & Moongkarndi, P.,  In-vivo Toxicity and Antitumor Activity of Mangosteen Extract, J. Nat. Med., 67(2): pp. 255–263, 2013.

Shibata,  M.A.,  Iinuma,  M.,  Morimoto,  J.,  Kurose,  H.,  Akamatsu,  K,  Okuno,  Y.,  Akao,  Y., & Otsuki, Y., Alpha-Mangostin Extracted  from the  Pericarp  of the Mangosteen  (Garcinia Mangostana  Linn)  Reduces  Tumor  Growth  and  Lymph  Node  Metastasis  ian Immunocompetent  Xenograft  Model  of  Metastatic  Mammary  Cancer  Carrying  A  P53 Mutation, B.M.C. Med., 9(69), 2011.

Sun, D., Zhang, S., Wei, Y., & Yin, L.,  Antioxidant Activity of Mangostin in Cell-Free System and Its Effect On K562 Leukemia Cell Line In Photodynamic Therapy, Acta Biochim. Biophys. Sin., 41(12), pp.1033-1043, 2009.

Padmavathi, R., Senthilnathan, P., Chodon, D., & Sakthisekaran, D., Therapeutic Effect of Paclitaxel and Propolis on Lipid Peroxidationa Antioxidant System in 7,12 Dimethyl, Benz(A)Anthracene-Induced Breast Cancer In Female Sprague, Dawley, Rats, Life Sci., 78(24), pp.2820-2825, 2006.

Mahmoud, N.N., Carothers, A.M., Grunberger, D., Bilinski, R.T., Churchill,  M.R., Martucci,  C., Newmark, H.L., & Bertagnolli, M.M., Plant Phenolics Decrease Intestinal Tumors in an Animal Model of Familial Adenomatous Polyposis, Carcinogenesis, 21(5), pp.921-927, 2000.

MacDonald, B.T., Tamai, K., & He, X., Wnt/b-Catenin Signaling: Components, Mechanisms, and Diseases, Dev. Cell., 17(1), pp. 9-26, 2009.

Chitchumroonchokchai, C. Thomas-Ahner, J.M., Li, J., Riedl, K.M., Nontakham, J., Suksumrarn, S., Clinton, S.K., Kinghorn, A.D., & Failla, M.L., Anti-tumorigenicity of Dietary α-mangostin in an HT-29 Colon Cell Xenograft Model and the Tissue Distribution of Xanthones and their Phase II Metabolites, Mol. Nutr. Food. Res., 57(2), pp. 203-211, 2013

Shih, Y.W., Chien, S.T., Chen, P.S., Lee, J.H., Wu, S.H., & Yin, L.T.,  α-Mangostin Suppresses Phorbol 12-myristate 13-acetate-Induced MMP-2/MMP-9 Expressions via αvβ3 Integrin/FAK/ERK and NF-κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells, Cell. Biochem. Biophys., 58(1), pp. 31–44, 2010.

Hattori, H., Okuda, K., Murase, T., Shigetsura, Y., Narise, K., Semenza, G.L., Nagasawa, H.., Isolation, Identification, and Biological Evaluation of HIF-1-modulating Compounds from Brazilian Green Propolis, Bioorg. Med. Chem., 19(18), pp. 5392-5401, 2011.

Paulino, N.., Abreu, S.R.L., Machado, G. & Silveira, E.,  Scientific Evidences to Pharmacological Anticancer Action of Baccharis Dracunculifolia Brazilian propolis, Rev. Pesq. Inov. Farm., 1(1), pp. 15-26, 2009.

Watanapokasin, R., Jarinthanan, F., Nakamura, Y., Sawasjirakij, N., Jaratrungtawee, A., & Suksamrarn, S., Effects of α-mangostin on Apoptosis Induction of Human Colon Cancer, World J. Gastroenterol, 17(16), pp.2086-2095, 2011.

Ishihara, M., Naoi, K., Hashita, M., Itoh, Y., & Suzui, M., Growth Inhibitory Activity of Ethanol Extracts of Chinese and Brazilian Propolis in Four Human Colon Carcinoma Cell Lines, Oncology Reports, 22(2), pp.349-354, 2009.

Kaur, B., Khwaja, F.W., Severson, E.A., Matheny, S.L., Brat, D.J., & Van Meir, E.G., Hypoxia and the Hypoxia-inducible-factor Pathway in Glioma Growth and Angiogenesis, Neuro. Oncol., 7(2), pp. 134-153, 2005.

Golubovskaya, V.M., Finch, R., Kweh, F., Massoll, N.A., Campbell-Thompson, M., Wallace, M.R., & Cance, W.G., p53 Regulates FAK Expression in Human Tumor Cells, Mol. Carcinogenesis, 47(5), pp.373–382, 2008.

Sadot, E., Geiger, B., Oren, M., & Ben-Ze’ev, A., Down-Regulation of β-Catenin by Activated p53, Mol. Cell. Biol., 21(20), pp. 6768–6781, 2001.

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