Skip to main content
Erschienen 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

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

Erschienen in: Tumor Biology | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
Metadaten
Titel
Alternol inhibits migration and invasion of human hepatocellular carcinoma cells by targeting epithelial-to-mesenchymal transition
verfasst von
Xiao-lin Zhu
Yan-li Wang
Jie-peng Chen
Li-li Duan
Pei-fang Cong
Ying-chun Qu
Jesse Li-Ling
Mei-xia Zhang
Publikationsdatum
01.02.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1224-y

Weitere Artikel der Ausgabe 2/2014

Tumor Biology 2/2014 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.