Curcumin suppresses migration and proliferation of Hep3B hepatocarcinoma cells through inhibition of the Wnt signaling pathway

Kim,Hyun  Jung; Park,Song  Yi; Park,Ock  Jin; Kim,Young‑Min

doi:10.3892/mmr.2013.1497

Curcumin suppresses migration and proliferation of Hep3B hepatocarcinoma cells through inhibition of the Wnt signaling pathway

Authors:
- Hyun Jung Kim
- Song Yi Park
- Ock Jin Park
- Young‑Min Kim
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Affiliations: Department of Biological Sciences and Biotechnology, Hannam University Daedeok Valley Campus, Daejeon 305‑811, Republic of Korea, Department of Food and Nutrition, Hannam University Daedeok Valley Campus, Daejeon 305‑811, Republic of Korea
Published online on: May 29, 2013 https://doi.org/10.3892/mmr.2013.1497
Pages: 282-286

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Abstract

Curcumin, the major phytochemical in turmeric, exerts anti‑proliferative, anticancer and anti‑inflammatory activities in various types of cancer cells. Curcumin has been demonstrated to induce apoptosis through multiple signaling pathways; however, its association with survival pathways, including the Wnt signaling pathway, is not fully understood. The Wnt signaling pathway is involved in diverse functions, including cell development, growth and proliferation. This pathway is important for cancer cell survival and metastasis. β‑catenin and GSK3β play a key role in the Wnt signaling pathway and therefore, various members of the Wnt signaling pathway have been hypothesized to represent potential targets for anticancer therapy. In the present study, the effect of curcumin on the suppression of migration and proliferation of Hep3B hepatocarcinoma cells was investigated via suppression of Wnt signaling in vitro and in vivo. 12‑O‑tetradecanoylphorbol‑13‑acetate (TPA)‑induced cell migration was observed to be suppressed by curcumin treatment. In addition, curcumin suppressed TPA‑induced activation of Wnt signaling. These results indicate that curcumin induces anti‑migratory activity, which functions via the Wnt signaling pathway.

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1	Surh YJ: Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 3:768–780. 2003. View Article : Google Scholar : PubMed/NCBI
2	Thangapazham RL, Sharma A and Maheshwari RK: Multiple molecular targets in cancer chemoprevention by curcumin. AAPS J. 8:443–449. 2006. View Article : Google Scholar : PubMed/NCBI
3	Johnson JJ and Mukhtar H: Curcumin for chemoprevention of colon cancer. Cancer Lett. 255:170–181. 2007. View Article : Google Scholar : PubMed/NCBI
4	Radhakrishna Pillai G, Srivastava AS, Hassanein TI, Chauhan DP and Carrier E: Induction of apoptosis in human lung cancer cells by curcumin. Cancer Lett. 208:163–170. 2004.PubMed/NCBI
5	Shi M, Cai Q, Yao L, Mao Y, Ming Y and Ouyang G: Antiproliferation and apoptosis induced by curcumin in human ovarian cancer cells. Cell Biol Int. 30:221–226. 2006. View Article : Google Scholar : PubMed/NCBI
6	Mehta K, Pantazis P, McQueen T and Aggarwal BB: Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell lines. Anticancer Drugs. 8:470–481. 1997. View Article : Google Scholar : PubMed/NCBI
7	Perry MC, Demeule M, Régina A, Moumdjian R and Béliveau R: Curcumin inhibits tumor growth and angiogenesis in glioblastoma xenografts. Mol Nutr Food Res. 54:1192–1201. 2010.PubMed/NCBI
8	Dujic J, Kippenberger S, Ramirez-Bosca A, Diaz-Alperi J, Bereiter-Hahn J, Kaufmann R, Bernd A and Hofmann M: Curcumin in combination with visible light inhibits tumor growth in a xenograft tumor model. Int J Cancer. 124:1422–1428. 2009. View Article : Google Scholar : PubMed/NCBI
9	Stagos D, Amoutzias GD, Matakos A, Spyrou A, Tsatsakis AM and Kouretas D: Chemoprevention of liver cancer by plant polyphenols. Food Chem Toxicol. 50:2155–2170. 2012. View Article : Google Scholar : PubMed/NCBI
10	Polakis P: Wnt signaling and cancer. Genes Dev. 14:1837–1851. 2000.
11	Fatima S, Lee NP and Luk JM: Dickkopfs and Wnt/β-catenin signalling in liver cancer. World J Clin Oncol. 2:311–325. 2011.
12	Esufali S and Bapat B: Cross-talk between Rac1 GTPase and dysregulated Wnt signaling pathway leads to cellular redistribution of beta-catenin and TCF/LEF-mediated transcriptional activation. Oncogene. 23:8260–8271. 2004. View Article : Google Scholar : PubMed/NCBI
13	Whittaker S, Marais R and Zhu AX: The role of signaling pathways in the development and treatment of hepatocellular carcinoma. Oncogene. 29:4989–5005. 2010. View Article : Google Scholar : PubMed/NCBI
14	Cadigan KM and Nusse R: Wnt signaling: a common theme in animal development. Genes Dev. 11:3286–3305. 1997. View Article : Google Scholar : PubMed/NCBI
15	Kim D and Chung J: Akt: versatile mediator of cell survival and beyond. J Biochem Mol Biol. 35:106–115. 2002. View Article : Google Scholar : PubMed/NCBI
16	Nojima H, Tokunaga C, Eguchi S, Oshiro N, Hidayat S, Yoshino K, Hara K, Tanaka N, Avruch J and Yonezawa K: The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem. 278:15461–15464. 2003. View Article : Google Scholar : PubMed/NCBI
17	Jung EM, Lim JH, Lee TJ, Park JW, Choi KS and Kwon TK: Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5). Carcinogenesis. 26:1905–1913. 2005. View Article : Google Scholar
18	Yu S, Shen G, Khor TO, Kim JH and Kong AN: Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism. Mol Cancer Ther. 7:2609–2620. 2008. View Article : Google Scholar : PubMed/NCBI
19	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
20	Chiu TL and Su CC: Curcumin inhibits proliferation and migration by increasing the Bax to Bcl-2 ratio and decrasing NF-Bp65 expression in breast cancer MDA-MB-231 cells. Int J Mol Med. 23:468–475. 2009.PubMed/NCBI
21	Shankar S and Srivastava RK: Involvement of Bcl-2 family members, phosphatidylinositol 3′-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer. Int J Oncol. 30:905–918. 2007.
22	Murayama K, Kimura T, Tarutani M, Tomooka M, Hayashi R, Okabe M, Nishida K, Itami S, Katayama I and Nakano T: Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors. Oncogene. 26:4882–4888. 2007. View Article : Google Scholar : PubMed/NCBI
23	Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, Wang CY, He X, MacDougald OA, You M, Williams BO and Guan KL: TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell. 126:955–968. 2006. View Article : Google Scholar : PubMed/NCBI
24	Chen RH, Ding WV and McCormick F: Wnt signaling to beta-catenin involves two interactive components. Glycogen synthase kinase-3beta inhibition and activation of protein kinase C. J Biol Chem. 275:17894–17899. 2000. View Article : Google Scholar : PubMed/NCBI
25	Dal Col J and Dolcetti R: GSK-3beta inhibition: at the crossroad between Akt and mTOR constitutive activation to enhance cyclin D1 protein stability in mantle cell lymphoma. Cell Cycle. 7:2813–2816. 2008.PubMed/NCBI