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Article

Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo

  • Authors:
    • Wanfu Lin
    • Maofeng Zhong
    • Huixia Yin
    • Yongan Chen
    • Qingxin Cao
    • Chen Wang
    • Changquan Ling
  • View Affiliations / Copyright

    Affiliations: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China
  • Pages: 961-967
    |
    Published online on: June 8, 2016
       https://doi.org/10.3892/or.2016.4861
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Abstract

Emodin is an active ingredient derived from root and rhizome of Rheum palmatum L and many studies have reported that it exhibits anticancer effects in a number of human tumors. However, there is little information demonstrating the possible effects of emodin on the proliferation and apoptosis of hepatocellular carcinoma (HCC). In the present study, we show that emodin may inhibit the proliferation of SMMC-7721 cells in a dose- and time-dependent manner and induced apoptosis of cells in a concentration-dependent manner after treatment for 24 h. Moreover, we further discovered that the possible molecular mechanisms involved may relate to the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Emodin may induce the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38 while mildly suppressed the expression of p-c-Jun-N-terminal kinase (p-JNK). However, emodin did not affect the expression of the total (t)-ERK, t-p38 or t-JNK. Furthermore, emodin also suppressed the activation of p-AKT, but not the t-AKT. In vivo, we found that emodin suppressed tumor growth in experimental mice without an obvious change in body weight, which may work through the antiproliferation and apoptosis inducing effects. Moreover, emodin improves the liver and kidney function in mice, revealing that emodin may improve the life quality of the mice with implanted tumors. In conclusion, the above findings indicate that emodin may be a potentially effective and safe drug to induce apoptosis of HCC.
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1 

Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, Allen C, Hansen G, Woodbrook R, Wolfe C, et al Global Burden of Disease Cancer Collaboration: The Global Burden of Cancer 2013. JAMA Oncol. 1:505–527. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Maluccio M and Covey A: Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Cancer J Clin. 62:394–399. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Ling CQ, Yue XQ and Ling C: Three advantages of using traditional Chinese medicine to prevent and treat tumor. J Integr Med. 12:331–335. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Block KI, Gyllenhaal C, Lowe L, Amedei A, Amin AR, Amin A, Aquilano K, Arbiser J, Arreola A, Arzumanyan A, et al: Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin Cancer Biol. 35(Suppl): S276–S304. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Xu H, Zhao X, Liu X, Xu P, Zhang K and Lin X: Antitumor effects of traditional Chinese medicine targeting the cellular apoptotic pathway. Drug Des Devel Ther. 9:2735–2744. 2015.PubMed/NCBI

6 

Wang X, Wang N, Cheung F, Lao L, Li C and Feng Y: Chinese medicines for prevention and treatment of human hepatocellular carcinoma: Current progress on pharmacological actions and mechanisms. J Integr Med. 13:142–164. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Qu W, Wang Y, Wu Q, Liu J and Hao D: Emodin inhibits HMGB1-induced tumor angiogenesis in human osteosarcoma by regulating SIRT1. Int J Clin Exp Med. 8:15054–15064. 2015.PubMed/NCBI

8 

Ma L and Li W: Emodin inhibits LOVO colorectal cancer cell proliferation via the regulation of the Bcl-2/Bax ratio and cytochrome c. Exp Ther Med. 8:1225–1228. 2014.PubMed/NCBI

9 

Xie MJ, Ma YH, Miao L, Wang Y, Wang HZ, Xing YY, Xi T and Lu YY: Emodin-provoked oxidative stress induces apoptosis in human colon cancer HCT116 cells through a p53-mitochondrial apoptotic pathway. Asian Pac J Cancer Prev. 15:5201–5205. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Yaoxian W, Hui Y, Yunyan Z, Yanqin L, Xin G and Xiaoke W: Emodin induces apoptosis of human cervical cancer HeLa cells via intrinsic mitochondrial and extrinsic death receptor pathway. Cancer Cell Int. 13:712013. View Article : Google Scholar : PubMed/NCBI

11 

Sun ZH and Bu P: Downregulation of phosphatase of regenerating liver-3 is involved in the inhibition of proliferation and apoptosis induced by emodin in the SGC-7901 human gastric carcinoma cell line. Exp Ther Med. 3:1077–1081. 2012.PubMed/NCBI

12 

Jia X, Yu F, Wang J, Iwanowycz S, Saaoud F, Wang Y, Hu J, Wang Q and Fan D: Emodin suppresses pulmonary metastasis of breast cancer accompanied with decreased macrophage recruitment and M2 polarization in the lungs. Breast Cancer Res Treat. 148:291–302. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Manu KA, Shanmugam MK, Ong TH, Subramaniam A, Siveen KS, Perumal E, Samy RP, Bist P, Lim LH, Kumar AP, et al: Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma. PLoS One. 8:e570152013. View Article : Google Scholar : PubMed/NCBI

14 

Sun Y, Wang X, Zhou Q, Lu Y, Zhang H, Chen Q, Zhao M and Su S: Inhibitory effect of emodin on migration, invasion and metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo. Oncol Rep. 33:338–346. 2015.

15 

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al SHARP Investigators Study Group: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Wei WT, Lin SZ, Liu DL and Wang ZH: The distinct mechanisms of the antitumor activity of emodin in different types of cancer (Review). Oncol Rep. 30:2555–2562. 2013.PubMed/NCBI

17 

Subramaniam A, Shanmugam MK, Ong TH, Li F, Perumal E, Chen L, Vali S, Abbasi T, Kapoor S, Ahn KS, et al: Emodin inhibits growth and induces apoptosis in an orthotopic hepatocellular carcinoma model by blocking activation of STAT3. Br J Pharmacol. 170:807–821. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Aroui S, Aouey B, Chtourou Y, Meunier AC, Fetoui H and Kenani A: Naringin suppresses cell metastasis and the expression of matrix metalloproteinases (MMP-2 and MMP-9) via the inhibition of ERK-P38-JNK signaling pathway in human glioblastoma. Chem Biol Interact. 244:195–203. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Yang M and Huang CZ: Mitogen-activated protein kinase signaling pathway and invasion and metastasis of gastric cancer. World J Gastroenterol. 21:11673–11679. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Yang SH, Sharrocks AD and Whitmarsh AJ: MAP kinase signalling cascades and transcriptional regulation. Gene. 513:1–13. 2013. View Article : Google Scholar

21 

Liu Y, Bi T, Dai W, Wang G, Qian L, Gao Q and Shen G: Oxymatrine synergistically enhances the inhibitory effect of 5-fluorouracil on hepatocellular carcinoma in vitro and in vivo. Tumour Biol. Dec 18–2015.Epub ahead of print.

22 

Chan LK, Chiu YT, Sze KM and Ng IO: Tensin4 is up-regulated by EGF-induced ERK1/2 activity and promotes cell proliferation and migration in hepatocellular carcinoma. Oncotarget. 6:20964–20976. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Zhao LY, Zhang J, Guo B, Yang J, Han J, Zhao XG, Wang XF, Liu LY, Li ZF, Song TS, et al: MECP2 promotes cell proliferation by activating ERK1/2 and inhibiting p38 activity in human hepatocellular carcinoma HEPG2 cells. Cell Mol Biol (Noisy-legrand). (Suppl 59): OL1876–OL1881. 2013.

24 

Lu WJ, Chua MS and So SK: Suppression of ATAD2 inhibits hepatocellular carcinoma progression through activation of p53- and p38-mediated apoptotic signaling. Oncotarget. 6:41722–41735. 2015.PubMed/NCBI

25 

Liu B, Yuan B, Zhang L, Mu W and Wang C: ROS/p38/p53/Puma signaling pathway is involved in emodin-induced apoptosis of human colorectal cancer cells. Int J Clin Exp Med. 8:15413–15422. 2015.PubMed/NCBI

26 

Liu W, Ning R, Chen RN, Huang XF, Dai QS, Hu JH, Wang YW, Wu LL, Xiong J, Hu G, et al: Aspafilioside B induces G2/M cell cycle arrest and apoptosis by up-regulating H-Ras and N-Ras via ERK and p38 MAPK signaling pathways in human hepatoma HepG2 cells. Mol Carcinog. 55:440–457. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Zhang C, Zhang J, Li X, Sun N, Yu R, Zhao B, Yu D, Cheng Y and Liu Y: Huaier aqueous extract induces hepatocellular carcinoma cells arrest in S phase via JNK signaling pathway. Evid Based Complement Alternat Med. 2015:1713562015. View Article : Google Scholar : PubMed/NCBI

28 

Wong KK, Engelman JA and Cantley LC: Targeting the PI3K signaling pathway in cancer. Curr Opin Genet Dev. 20:87–90. 2010. View Article : Google Scholar :

29 

Engelman JA: Targeting PI3K signalling in cancer: Opportunities, challenges and limitations. Nat Rev Cancer. 9:550–562. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Kunter I, Erdal E, Nart D, Yilmaz F, Karademir S, Sagol O and Atabey N: Active form of AKT controls cell proliferation and response to apoptosis in hepatocellular carcinoma. Oncol Rep. 31:573–580. 2014.

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Copy and paste a formatted citation
Spandidos Publications style
Lin W, Zhong M, Yin H, Chen Y, Cao Q, Wang C and Ling C: Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo. Oncol Rep 36: 961-967, 2016.
APA
Lin, W., Zhong, M., Yin, H., Chen, Y., Cao, Q., Wang, C., & Ling, C. (2016). Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo. Oncology Reports, 36, 961-967. https://doi.org/10.3892/or.2016.4861
MLA
Lin, W., Zhong, M., Yin, H., Chen, Y., Cao, Q., Wang, C., Ling, C."Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo". Oncology Reports 36.2 (2016): 961-967.
Chicago
Lin, W., Zhong, M., Yin, H., Chen, Y., Cao, Q., Wang, C., Ling, C."Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo". Oncology Reports 36, no. 2 (2016): 961-967. https://doi.org/10.3892/or.2016.4861
Copy and paste a formatted citation
x
Spandidos Publications style
Lin W, Zhong M, Yin H, Chen Y, Cao Q, Wang C and Ling C: Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo. Oncol Rep 36: 961-967, 2016.
APA
Lin, W., Zhong, M., Yin, H., Chen, Y., Cao, Q., Wang, C., & Ling, C. (2016). Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo. Oncology Reports, 36, 961-967. https://doi.org/10.3892/or.2016.4861
MLA
Lin, W., Zhong, M., Yin, H., Chen, Y., Cao, Q., Wang, C., Ling, C."Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo". Oncology Reports 36.2 (2016): 961-967.
Chicago
Lin, W., Zhong, M., Yin, H., Chen, Y., Cao, Q., Wang, C., Ling, C."Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo". Oncology Reports 36, no. 2 (2016): 961-967. https://doi.org/10.3892/or.2016.4861
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