Skip to main content
Top
Published in: Tumor Biology 2/2014

01-02-2014 | Research Article

Alternol inhibits migration and invasion of human hepatocellular carcinoma cells by targeting epithelial-to-mesenchymal transition

Authors: Xiao-lin Zhu, Yan-li Wang, Jie-peng Chen, Li-li Duan, Pei-fang Cong, Ying-chun Qu, Jesse Li-Ling, Mei-xia Zhang

Published in: Tumor Biology | Issue 2/2014

Login to get access

Abstract

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. Such deaths are due, in large part, to its propensity to metastasize. We have examined the effect of alternol on human HCC cells and the underlying molecular mechanism. Therapeutic effects of alternol on cancer cell migration and invasion were analyzed with Boyden chamber and wound healing assays. Effects of alternol on the levels of various proteins involved in cancer cell migration and invasion were determined with gelatin zymography, immunofluorescence, and Western blotting. As shown, treatment with alternol has resulted in a concentration-dependent inhibition of cell migration and invasion of HepG2 cells. The inhibition of HCC invasion by alternol was associated with the suppression of MMP-9 expression and reversal of epithelial-to-mesenchymal transition (EMT). The above results indicated that alternol has the ability to inhibit the migration and invasion of human HCC cells by reversing the process of EMT, suggesting that alternol may be developed as an alternative drug for the treatment of HCC.
Literature
1.
go back to reference Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47(Suppl):S2–6.PubMedCrossRef Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47(Suppl):S2–6.PubMedCrossRef
2.
go back to reference Wong KF, Xu Z, Chen J, Lee NP, Luk JM. Circulating markers for prognosis of hepatocellular carcinoma. Expert Opin Med Diagn. 2013;7:319–29.PubMedCrossRef Wong KF, Xu Z, Chen J, Lee NP, Luk JM. Circulating markers for prognosis of hepatocellular carcinoma. Expert Opin Med Diagn. 2013;7:319–29.PubMedCrossRef
3.
go back to reference Aravalli RN, Cressman EN, Steer CJ. Cellular and molecular mechanisms of hepatocellular carcinoma: an update. Arch Toxicol. 2013;87:227–47.PubMedCrossRef Aravalli RN, Cressman EN, Steer CJ. Cellular and molecular mechanisms of hepatocellular carcinoma: an update. Arch Toxicol. 2013;87:227–47.PubMedCrossRef
4.
go back to reference Psyrri A, Arkadopoulos N, Vassilakopoulou M, Smyrniotis V, Dimitriadis G. Pathways and targets in hepatocellular carcinoma. Expert Rev Anticancer Ther. 2012;12:1347–57.PubMedCrossRef Psyrri A, Arkadopoulos N, Vassilakopoulou M, Smyrniotis V, Dimitriadis G. Pathways and targets in hepatocellular carcinoma. Expert Rev Anticancer Ther. 2012;12:1347–57.PubMedCrossRef
5.
go back to reference Fortune BE, Umman V, Gilliland T, Emre S. Liver transplantation for hepatocellular carcinoma: a surgical perspective. J Clin Gastroenterol. 2013;47(Suppl):S37–42.PubMedCrossRef Fortune BE, Umman V, Gilliland T, Emre S. Liver transplantation for hepatocellular carcinoma: a surgical perspective. J Clin Gastroenterol. 2013;47(Suppl):S37–42.PubMedCrossRef
6.
go back to reference Padhya KT, Marrero JA, Singal AG. Recent advances in the treatment of hepatocellular carcinoma. Curr Opin Gastroenterol. 2013;29:285–92.PubMedCrossRef Padhya KT, Marrero JA, Singal AG. Recent advances in the treatment of hepatocellular carcinoma. Curr Opin Gastroenterol. 2013;29:285–92.PubMedCrossRef
9.
go back to reference Salhab M, Canelo R. An overview of evidence-based management of hepatocellular carcinoma: a meta-analysis. J Cancer Res Ther. 2011;7:463–75.PubMedCrossRef Salhab M, Canelo R. An overview of evidence-based management of hepatocellular carcinoma: a meta-analysis. J Cancer Res Ther. 2011;7:463–75.PubMedCrossRef
10.
go back to reference Hamed O, Kimchi ET, Sehmbey M, Gusani NJ, Kaifi JT, Staveley-O’Carroll K. Impact of genetic targets on cancer therapy: hepatocellular cancer. Adv Exp Med Biol. 2013;779:67–90.PubMedCrossRef Hamed O, Kimchi ET, Sehmbey M, Gusani NJ, Kaifi JT, Staveley-O’Carroll K. Impact of genetic targets on cancer therapy: hepatocellular cancer. Adv Exp Med Biol. 2013;779:67–90.PubMedCrossRef
11.
go back to reference Subramaniam A, Shanmugam MK, Perumal E, Li F, Nachiyappan A, Dai X, et al. Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma. Biochim Biophys Acta. 1835;2013:46–60. Subramaniam A, Shanmugam MK, Perumal E, Li F, Nachiyappan A, Dai X, et al. Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma. Biochim Biophys Acta. 1835;2013:46–60.
12.
go back to reference Muntane J, De la Rosa AJ, Docobo F, Garcia-Carbonero R, Padillo FJ. Targeting tyrosine kinase receptors in hepatocellular carcinoma. Curr Cancer Drug Targets. 2013;13:300–12.PubMedCrossRef Muntane J, De la Rosa AJ, Docobo F, Garcia-Carbonero R, Padillo FJ. Targeting tyrosine kinase receptors in hepatocellular carcinoma. Curr Cancer Drug Targets. 2013;13:300–12.PubMedCrossRef
13.
go back to reference Ganapathy-Kanniappan S, Kunjithapatham R, Geschwind JF. Glyceraldehyde-3-phosphate dehydrogenase: a promising target for molecular therapy in hepatocellular carcinoma. Oncotarget. 2012;3:940–53.PubMed Ganapathy-Kanniappan S, Kunjithapatham R, Geschwind JF. Glyceraldehyde-3-phosphate dehydrogenase: a promising target for molecular therapy in hepatocellular carcinoma. Oncotarget. 2012;3:940–53.PubMed
14.
go back to reference Katsuno Y, Lamouille S, Derynck R. TGF-beta signaling and epithelial-mesenchymal transition in cancer progression. Curr Opin Oncol. 2013;25:76–84.PubMedCrossRef Katsuno Y, Lamouille S, Derynck R. TGF-beta signaling and epithelial-mesenchymal transition in cancer progression. Curr Opin Oncol. 2013;25:76–84.PubMedCrossRef
15.
go back to reference Ramakrishna R, Rostomily R. Seed, soil, and beyond: the basic biology of brain metastasis. Surg Neurol Int. 2013;4 (Suppl 4):S256–64. Ramakrishna R, Rostomily R. Seed, soil, and beyond: the basic biology of brain metastasis. Surg Neurol Int. 2013;4 (Suppl 4):S256–64.
16.
go back to reference Reichl P, Haider C, Grubinger M, Mikulits W. TGF-beta in epithelial to mesenchymal transition and metastasis of liver carcinoma. Curr Pharm Des. 2012;18:4135–47.PubMedCrossRef Reichl P, Haider C, Grubinger M, Mikulits W. TGF-beta in epithelial to mesenchymal transition and metastasis of liver carcinoma. Curr Pharm Des. 2012;18:4135–47.PubMedCrossRef
17.
go back to reference Chang TM, Hung WC. Transcriptional repression of TWIST1 gene by Prospero-related homeobox 1 inhibits invasiveness of hepatocellular carcinoma cells. FEBS Lett. 2012;586:3746–52.PubMedCrossRef Chang TM, Hung WC. Transcriptional repression of TWIST1 gene by Prospero-related homeobox 1 inhibits invasiveness of hepatocellular carcinoma cells. FEBS Lett. 2012;586:3746–52.PubMedCrossRef
18.
go back to reference Qin Q, Xu Y, He T, Qin C, Xu J. Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms. Cell Res. 2012;22:90–106.PubMedCrossRef Qin Q, Xu Y, He T, Qin C, Xu J. Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms. Cell Res. 2012;22:90–106.PubMedCrossRef
19.
go back to reference Matsuo N, Shiraha H, Fujikawa T, Takaoka N, Ueda N, Tanaka S, et al. Twist expression promotes migration and invasion in hepatocellular carcinoma. BMC Cancer. 2009;9:240.PubMedCentralPubMedCrossRef Matsuo N, Shiraha H, Fujikawa T, Takaoka N, Ueda N, Tanaka S, et al. Twist expression promotes migration and invasion in hepatocellular carcinoma. BMC Cancer. 2009;9:240.PubMedCentralPubMedCrossRef
20.
go back to reference Yeung ED, Morrison A, Plumeri D, Wang J, Tong C, Yan X, et al. Alternol exerts prostate-selective antitumor effects through modulations of the AMPK signaling pathway. Prostate. 2012;72:165–72.PubMedCrossRef Yeung ED, Morrison A, Plumeri D, Wang J, Tong C, Yan X, et al. Alternol exerts prostate-selective antitumor effects through modulations of the AMPK signaling pathway. Prostate. 2012;72:165–72.PubMedCrossRef
21.
go back to reference Liu X, Wang J, Sun B, Zhang Y, Zhu J, Li C. Cell growth inhibition, G2M cell cycle arrest, and apoptosis induced by the novel compound Alternol in human gastric carcinoma cell line MGC803. Invest New Drugs. 2007;25:505–17.PubMedCrossRef Liu X, Wang J, Sun B, Zhang Y, Zhu J, Li C. Cell growth inhibition, G2M cell cycle arrest, and apoptosis induced by the novel compound Alternol in human gastric carcinoma cell line MGC803. Invest New Drugs. 2007;25:505–17.PubMedCrossRef
22.
go back to reference Liu ZZ, Zhu J, Sun B, Liu S, Geng S, Liu X, et al. Alternol inhibits proliferation and induces apoptosis in mouse lymphocyte leukemia (L1210) cells. Mol Cell Biochem. 2007;306:115–22.PubMedCrossRef Liu ZZ, Zhu J, Sun B, Liu S, Geng S, Liu X, et al. Alternol inhibits proliferation and induces apoptosis in mouse lymphocyte leukemia (L1210) cells. Mol Cell Biochem. 2007;306:115–22.PubMedCrossRef
23.
go back to reference Shih YW, Lee YC, Wu PF, Lee YB, Chiang TA. Plumbagin inhibits invasion and migration of liver cancer HepG2 cells by decreasing productions of matrix metalloproteinase-2 and urokinase- plasminogen activator. Hepatol Res. 2009;39:998–1009.PubMedCrossRef Shih YW, Lee YC, Wu PF, Lee YB, Chiang TA. Plumbagin inhibits invasion and migration of liver cancer HepG2 cells by decreasing productions of matrix metalloproteinase-2 and urokinase- plasminogen activator. Hepatol Res. 2009;39:998–1009.PubMedCrossRef
24.
go back to reference Li X, Yang Z, Song W, Zhou L, Li Q, Tao K, et al. Overexpression of Bmi-1 contributes to the invasion and metastasis of hepatocellular carcinoma by increasing the expression of matrix metalloproteinase (MMP)2, MMP-9 and vascular endothelial growth factor via the PTEN/PI3K/Akt pathway. Int J Oncol. 2013;43:793–802.PubMed Li X, Yang Z, Song W, Zhou L, Li Q, Tao K, et al. Overexpression of Bmi-1 contributes to the invasion and metastasis of hepatocellular carcinoma by increasing the expression of matrix metalloproteinase (MMP)2, MMP-9 and vascular endothelial growth factor via the PTEN/PI3K/Akt pathway. Int J Oncol. 2013;43:793–802.PubMed
25.
go back to reference Sun C, Sun L, Li Y, Kang X, Zhang S, Liu Y. Sox2 expression predicts poor survival of hepatocellular carcinoma patients and it promotes liver cancer cell invasion by activating Slug. Med Oncol. 2013;30:503.PubMedCrossRef Sun C, Sun L, Li Y, Kang X, Zhang S, Liu Y. Sox2 expression predicts poor survival of hepatocellular carcinoma patients and it promotes liver cancer cell invasion by activating Slug. Med Oncol. 2013;30:503.PubMedCrossRef
26.
go back to reference Slattery ML, John E, Torres-Mejia G, Stern M, Lundgreen A, Hines L, et al. Matrix metalloproteinase genes are associated with breast cancer risk and survival: the Breast Cancer Health Disparities Study. PLoS One. 2013;8:e63165.PubMedCentralPubMedCrossRef Slattery ML, John E, Torres-Mejia G, Stern M, Lundgreen A, Hines L, et al. Matrix metalloproteinase genes are associated with breast cancer risk and survival: the Breast Cancer Health Disparities Study. PLoS One. 2013;8:e63165.PubMedCentralPubMedCrossRef
27.
go back to reference Littlepage LE, Sternlicht MD, Rougier N, Phillips J, Gallo E, Yu Y, et al. Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression. Cancer Res. 2010;70:2224–34.PubMedCentralPubMedCrossRef Littlepage LE, Sternlicht MD, Rougier N, Phillips J, Gallo E, Yu Y, et al. Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression. Cancer Res. 2010;70:2224–34.PubMedCentralPubMedCrossRef
28.
go back to reference Lou L, Chen YX, Jin L, Li X, Tao X, Zhu J, et al. Enhancement of invasion of hepatocellular carcinoma cells through lysophosphatidic acid receptor. J Int Med Res. 2013;41:55–63.PubMedCrossRef Lou L, Chen YX, Jin L, Li X, Tao X, Zhu J, et al. Enhancement of invasion of hepatocellular carcinoma cells through lysophosphatidic acid receptor. J Int Med Res. 2013;41:55–63.PubMedCrossRef
29.
go back to reference Yang X, Wang D, Dong W, Song Z, Dou K. Inhibition of Na(+)/H(+) exchanger 1 by 5-(N-ethyl-N-isopropyl) amiloride reduces hypoxia-induced hepatocellular carcinoma invasion and motility. Cancer Lett. 2010;295:198–204.PubMedCrossRef Yang X, Wang D, Dong W, Song Z, Dou K. Inhibition of Na(+)/H(+) exchanger 1 by 5-(N-ethyl-N-isopropyl) amiloride reduces hypoxia-induced hepatocellular carcinoma invasion and motility. Cancer Lett. 2010;295:198–204.PubMedCrossRef
30.
go back to reference Pan MH, Chiou YS, Chen WJ, Wang JM, Badmaev V, Ho CT. Pterostilbene inhibited tumor invasion via suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. Carcinogenesis. 2009;30:1234–42.PubMedCrossRef Pan MH, Chiou YS, Chen WJ, Wang JM, Badmaev V, Ho CT. Pterostilbene inhibited tumor invasion via suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. Carcinogenesis. 2009;30:1234–42.PubMedCrossRef
31.
go back to reference Li X, Xu Y, Chen Y, Chen S, Jia X, Sun T, et al. SOX2 promotes tumor metastasis by stimulating epithelial-to-mesenchymal transition via regulation of WNT/beta-catenin signal network. Cancer Lett. 2013;336:379–89.PubMedCrossRef Li X, Xu Y, Chen Y, Chen S, Jia X, Sun T, et al. SOX2 promotes tumor metastasis by stimulating epithelial-to-mesenchymal transition via regulation of WNT/beta-catenin signal network. Cancer Lett. 2013;336:379–89.PubMedCrossRef
32.
go back to reference van Zijl F, Zulehner G, Petz M, Schneller D, Kornauth C, Hau M, et al. Epithelial–mesenchymal transition in hepatocellular carcinoma. Future Oncol. 2009;5:1169–79.PubMedCrossRef van Zijl F, Zulehner G, Petz M, Schneller D, Kornauth C, Hau M, et al. Epithelial–mesenchymal transition in hepatocellular carcinoma. Future Oncol. 2009;5:1169–79.PubMedCrossRef
Metadata
Title
Alternol inhibits migration and invasion of human hepatocellular carcinoma cells by targeting epithelial-to-mesenchymal transition
Authors
Xiao-lin Zhu
Yan-li Wang
Jie-peng Chen
Li-li Duan
Pei-fang Cong
Ying-chun Qu
Jesse Li-Ling
Mei-xia Zhang
Publication date
01-02-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1224-y

Other articles of this Issue 2/2014

Tumor Biology 2/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine