Anti-proliferation and Insulin Resistance Alleviation of Hepatocellular Carcinoma Cells HepG2 in Vitro by Chinese Propolis

Yazhou Zhao¹, Wenli Tian¹ and Wenjun Peng^1,

¹Institute of Apiculture, Chinese Academy of Agricultural Sciences, Beijing, China

Cite this paper:
Yazhou Zhao, Wenli Tian and Wenjun Peng. Anti-proliferation and Insulin Resistance Alleviation of Hepatocellular Carcinoma Cells HepG2 in Vitro by Chinese Propolis. Journal of Food and Nutrition Research. 2014; 2(5):228-235. doi: 10.12691/jfnr-2-5-4

Abstract

Previous studies suggest affirmative effects of propolis on cancers and diabetes, due to its abundant flavonids. But information is rarely available with regard to its effects on hepatocellular carcinoma cells (HCC), particularly on cell proliferation and insulin resistance (IR). We measured the flavonids of ethanol extract from Chinese propolis (EEP) by HPLC. IR model of HepG2 cells were established, which were treated with different kinds and doses of propolis. The anti-proliferation and IR alleviation of HepG2 cells were studied. As result, EEP contained many flavonoids. Compared with other two solvents (PEG and DMSO), olive oil (dosage: 200 μg/mL) could significantly inhibit cell proliferation and alleviate IR of HepG2 cells. EEP dissolved in DMSO (mass ratio: 2:1; dosage: 300 μg/mL) exhibited anti-proliferative effect on HepG2 cells. When EEP was dissolved in olive oil (mass ratio: 2:1; dosage: 300 μg/mL), IR of HepG2 cells was greatly alleviated. As a conclusion, olive oil may be more suitable as auxiliary solvent of propolis as to improve its biological activities. High-dose propolis could effectively inhibit the proliferation and alleviate the IR of HepG2 cells in vitro.

Keywords:
cell proliferation flavonoids HepG2 cells insulin resistance propolis

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References:

[1]	El-Serag, H.B., Marrero, J.A., Rudolph, L. and Reddy, K.R, “Diagnosis and treatment of hepatocellular carcinoma,” Gastroenterology, 134(6), 1752-1763. May 2008.
[2]	Bruix, J., and Sherman, M, “Management of hepatocellular carcinoma: an update,” Hepatology, 53(3), 1020-1022. Mar. 2011.
[3]	Baiz, D., Pozzato, G., Dapas, B., Farra, R., Scaggiante, B., Grassi, M. and Grassi, G, “Bortezomib arrests the proliferation of hepatocellular carcinoma cells HepG2 and JHH6 by differentially affecting E2F1, p21 and p27 levels,” Biochimie, 91(3), 373-382. Mar. 2009.
[4]	Absood, A., Hu, B., Bassily, N., and Colletti, L, “VIP inhibits human HepG2 cell proliferation in vitro,” Regulatory Peptides, 146(1), 285-292. Feb. 2008.
[5]	Fernández-Real, J.M., and Pickup, J.C, “Innate immunity, insulin resistance and type 2 diabetes,” Trends in Endocrinology & Metabolism, 19(1), 10-16. Jan. 2008.
[6]	Haffner, S.M., Valdez, R.A., Hazuda, H.P., Mitchell, B.D., Morales, P.A., and Stern, M.P, “Prospective analysis of the insulin-resistance syndrome (syndrome X),” Diabetes, 41(6), 715-722. Jun. 1992.
[7]	Zhang, W.Y., Lee, J.J., Kim, I.S., Kim, Y., Park, J.S., and Myung, C.S, “7-O-Methylaromadendrin stimulates glucose uptake and improves insulin resistance in vitro,” Biological and Pharmaceutical Bulletin, 33(9), 1494-1499. Sep. 2010.
[8]	Zhang, W.Y., Lee, J.J., Kim, Y., Kim, I.S., Han, J.H., Lee, S.G. and Myung, C.S, “Effect of eriodictyol on glucose uptake and insulin resistance in vitro,” Journal of agricultural and food chemistry, 60(31), 7652-7658. Jul. 2012.
[9]	El-Sayed, E.S., Abo-Salem, O.M., Aly, H.A. and Mansour, A.M, “Potential antidiabetic and hypolipidemic effects of propolis extract in streptozotocin-induced diabetic rats,” Pakistan Journal of Pharmaceutical Sciences, 22, 168-174. 2009.
[10]	Kang, L.J., Lee, H.B., Bae, H.J. and Lee, S.G, “Antidiabetic effect of propolis: reduction of expression of glucose-6-phosphatase through inhibition of Y279 and Y216 autophosphorylation of GSK‐3α/β in HepG2 cells,” Phytotherapy research, 24(10), 1554-1561. Oct. 2010.
[11]	Moţ, A.C., Soponar, F. and Sârbu, C, “Multivariate analysis of reflectance spectra from propolis: Geographical variation in Romanian samples,” Talanta, 81(3), 1010-1015. May 2010.
[12]	Simone-Finstrom, M., and Spivak, M, “Propolis and bee health: the natural history and significance of resin use by honey bees,” Apidologie, 41(3), 295-311. May 2007.
[13]	Sipos, P., Gyõry, H., Hagymási, K., Ondrejka, P. and Blázovics, A, “Special wound healing methods used in ancient Egypt and the mythological background,” World Journal of Surgery, 28(2), 211-216. Feb. 2004.
[14]	Burdock, G.A, “Review of the biological properties and toxicity of bee propolis (propolis),” Food Chemical Toxicology, 36(4), 347-363. Apr. 1998.
[15]	Bankova, V.S., de Castro, S.L. and Marcucci, M.C, “Propolis: recent advances in chemistry and plant origin,” Apidologie, 31(1), 3-16. Jan.-Feb. 2000.
[16]	Szliszka, E., Zydowicz, G., Janoszka, B., Dobosz, C., Kowalczyk-Ziomek, G. and Krol, W, “Ethanolic extract of Brazilian green propolis sensitizes prostate cancer cells to TRAIL-induced apoptosis,” International Journal of Oncology, 38(4), 941-953. Apr. 2011.
[17]	Mouse, H.A., Tilaoui, M., Jaafari, A., M'barek, L.A., Aboufatima, R., Chait, A. and Zyad, A, “Evaluation of the in vitro and in vivo anticancer properties of Moroccan propolis extracts,” Revista Brasileira de Farmacognosia, 22(3), 558-567. May-Jun. 2012.
[18]	Bankova, V, “Chemical diversity of propolis and the problem of standardization,” Journal of Ethnopharmacology, 100(1), 114-117. Aug. 2005.
[19]	Kujumgiev, A., Tsvetkova, I., Serkedjieva, Y., Bankova, V., Christov, R. and Popov, S, “Antibacterial, antifungal and antiviral activity of propolis of different geographic origin,” Journal of Ethnopharmacology, 64(3), 235-240. Mar. 1999.
[20]	Uzel, A., Sorkun, K., Önçağ, Ö., Çoğulu, D. and Gençay, Ö, “Chemical compositions and antimicrobial activities of four different Anatolian propolis samples,” Microbiological Research, 160(2), 189-195. Apr. 2005.
[21]	Ahn, M.R., Kumazawa, S., Usui, Y., Nakamura, J., Matsuka, M., Zhu, F. and Nakayama, T, “Antioxidant activity and constituents of propolis collected in various areas of China,” Food Chemistry, 101(4), 1383-1392. 2007.
[22]	Ahn, M.R., Kunimasa, K., Kumazawa, S., Nakayama, T., Kaji, K., Uto, Y. and Ohta, T, “Correlation between antiangiogenic activity and antioxidant activity of various components from propolis,” Molecular Nutrition & Food Research, 53(5), 643-651. May 2009.
[23]	Kimoto, T., Arai, S., Kohguchi, M., Aga, M., Nomura, Y., Micallef, M.J. and Mito, K, “Apoptosis and suppression of tumor growth by artepillin C extracted from Brazilian propolis,” Cancer detection and prevention, 22(6), 506-515. 1998.
[24]	Zamami, Y., Takatori, S., Koyama, T., Goda, M., Iwatani, Y. and Kawasaki, H, “Effect of propolis on insulin resistance in fructose-drinking rats,” Yakugaku zasshi: Journal of the Pharmaceutical Society of Japan, 127(12), 2065-2073. 2007.
[25]	Koya-Miyata, S., Arai, N., Mizote, A., Taniguchi, Y., Ushio, S., Iwaki, K. and Fukuda, S, “Propolis prevents diet-induced hyperlipidemia and mitigates weight gain in diet-induced obesity in mice,” Biological and Pharmaceutical Bulletin, 32(12), 2022-2028. Dec. 2009.
[26]	Tian, W.L., Zhao, Y.Z., Fang, X.M., Gao, L.Y. and Peng, W.J, “Analysis of volatile components in ethanolic extract of propolis,” Modern Food Science and Technology, 28, 456-461, 475. Apr. 2012.
[27]	Popova, M.P., Bankova, V.S., Bogdanov, S., Tsvetkova, I., Naydenski, C., Marcazzan, G.L. and Sabatini, A.G, “Chemical characteristics of poplar type propolis of different geographic origin,” Apidologie, 38(3), 306-311. May 2007.
[28]	Bufalo, M.C., Candeias, J.M. and Sforcin, J.M, “In vitro cytotoxic effect of Brazilian green propolis on human laryngeal epidermoid carcinoma (HEp-2) cells,” Evidence-Based Complementary and Alternative Medicine, 6(4), 483-487. 2009.
[29]	Sonmez, S., Kirilmaz, L., Yucesoy, M., Yücel, B. and Yilmaz, B, “The effect of bee propolis on oral pathogens and human gingival fibroblasts,” Journal of Ethnopharmacology, 102(3), 371-376. Dec. 2005.
[30]	Noori, A.L., Al-Ghamdi, A., Ansari, M.J., Al-Attal, Y. and Salom, K, “Synergistic effects of honey and propolis toward drug multi-resistant Staphylococcus aureus, Escherichia coli and Candida albicans isolates in single and polymicrobial cultures,” International Journal of Medical Sciences, 9(9), 793-800. Oct. 2012.
[31]	Chen, S.L, The Apicultural Science in China, China Agriculture Press, Beijing, 2001, 666.