Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
June-2022 Volume 60 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2022 Volume 60 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data1.pdf
    • Supplementary_Data2.pdf
Article Open Access

Chimeric HDAC and the cytoskeleton inhibitor broxbam as a novel therapeutic strategy for liver cancer

  • Authors:
    • Sofia Isolde Bär
    • Alexandra Dittmer
    • Bianca Nitzsche
    • Gohar Ter-Avetisyan
    • Michael Fähling
    • Adrian Klefenz
    • Leonard Kaps
    • Bernhard Biersack
    • Rainer Schobert
    • Michael Höpfner
  • View Affiliations / Copyright

    Affiliations: Organic Chemistry Laboratory, University of Bayreuth, D-95447 Bayreuth, Germany, Institute of Physiology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, D-10117 Berlin, Germany, Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, D-10117 Berlin, Germany, Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, D-10117 Berlin, Germany, Institute of Translational Immunology, University Medical Center of the Johannes Gutenberg University, D-55131 Mainz, Germany
    Copyright: © Bär et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 73
    |
    Published online on: April 28, 2022
       https://doi.org/10.3892/ijo.2022.5363
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Broxbam, also known as N-hydroxy-4-{1-methoxy-4-[4'-(3'-bromo-4',5'-dimethoxyphenyl)-oxazol-5'-yl]-2-phenoxy} butanamide, is a novel chimeric inhibitor that contains two distinct pharmacophores in its molecular structure. It has been previously demonstrated to inhibit the activity of histone deacetylases (HDAC) and tubulin polymerisation, two critical components required for cancer growth and survival. In the present study, the potential suitability of broxbam for the treatment of liver cancer was investigated. The effects of broxbam on cell proliferation and apoptosis, in addition to the underlying molecular mechanism of action, were first investigated in primary liver cancer cell lines Huh7, HepG2, TFK1 and EGI1. Real-time proliferation measurements made using the iCELLigence system and viable cell number counting following crystal violet staining) revealed that broxbam time- and dose-dependently reduced the proliferation of liver cancer cell lines with IC50 values <1 µM. In addition, a significant inhibition of the growth of hepatoblastoma microtumours on the chorioallantoic membranes (CAM) of fertilised chicken eggs by broxbam was observed according to results from the CAM assay, suggesting antineoplastic potency in vivo. Broxbam also exerted apoptotic effects through p53- and mitochondria-driven caspase-3 activation in Huh7 and HepG2 cells according to data from western blotting (p53 and phosphorylated p53), mitochondrial membrane potential measurements (JC-1 assay) and fluorometric capsase-3 measurements. Notably, no contribution of unspecific cytotoxic effects mediated by broxbam were observed from LDH-release measurements. HDAC1, -2, -4 and -6 expression was measured by western blotting and the HDAC inhibitory potency of broxbam was next evaluated using subtype-specific HDAC enzymatic assays, which revealed a largely pan-HDAC inhibitory activity with the most potent inhibition observed on HDAC6. Silencing HDAC6 expression in Huh7 cells led to a drop in the expression of the proliferation markers Ki-67 and E2F3, suggesting that HDAC6 inhibition by broxbam may serve a predominant role in their antiproliferative effects on liver cancer cells. Immunofluorescence staining of cytoskeletal proteins (α-tubulin & actin) of broxbam-treated HepG2 cells revealed a pronounced inhibition of tubulin polymerisation, which was accompanied by reduced cell migration as determined by wound healing scratch assays. Finally, data from zebrafish angiogenesis assays revealed marked antiangiogenic effects of broxbam in vivo, as shown by the suppression of subintestinal vein growth in zebrafish embryos. To conclude, the pleiotropic anticancer activities of this novel chimeric HDAC- and tubulin inhibitor broxbam suggest that this compound is a promising candidate for liver cancer treatment, which warrants further pre-clinical and clinical evaluation.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

View References

1 

Siegel RL, Miller KD, Fuchs HE and Jemal A: Cancer statistics, 2021. CA Cancer J Clin. 71:7–33. 2021. View Article : Google Scholar : PubMed/NCBI

2 

Mosconi S, Beretta GD, Labianca R, Zampino MG, Gatta G and Heinemann V: Cholangiocarcinoma. Crit Rev Oncol Hematol. 69:259–270. 2009. View Article : Google Scholar

3 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Vogel A, Cervantes A, Chau I, Daniele B, Llovet JM, Meyer T, Nault JC, Neumann U, Ricke J, Sangro B, et al: Hepatocellular carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 29(Suppl 4): iv238–iv255. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Lim H, Ramjeesingh R, Liu D, Tam VC, Knox JJ, Card PB and Meyers BM: Optimizing survival and the changing landscape of targeted therapy for intermediate and advanced hepatocellular carcinoma: A systematic review. J Natl Cancer Inst. 113:123–136. 2021. View Article : Google Scholar :

6 

Li Y, Gao ZH and Qu XJ: The adverse effects of sorafenib in patients with advanced cancers. Basic Clin Pharmacol Toxicol. 116:216–221. 2015. View Article : Google Scholar

7 

Tang W, Chen Z, Zhang W, Cheng Y, Zhang B, Wu F, Wang Q, Wang S, Rong D, Reiter FP, et al: The mechanisms of sorafenib resistance in hepatocellular carcinoma: Theoretical basis and therapeutic aspects. Sig Transduct Target Ther. 5:872020. View Article : Google Scholar

8 

Doherty B, Nambudiri VE and Palmer WC: Update on the diagnosis and treatment of cholangiocarcinoma. Curr Gastroenterol Rep. 19:22017. View Article : Google Scholar : PubMed/NCBI

9 

Morise Z, Sugioka A, Tokoro T, Tanahashi Y, Okabe Y, Kagawa T and Takeura C: Surgery and chemotherapy for intrahepatic cholangiocarcinoma. World J Hepatol. 2:58–64. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Goehringer N, Biersack B, Peng Y, Schobert R, Herling M, Ma A, Nitzsche B and Höpfner M: Anticancer activity and mechanisms of action of new chimeric EGFR/HDAC-inhibitors. Int J Mol Sci. 22:84322021. View Article : Google Scholar : PubMed/NCBI

11 

Biersack B, Polat S and Höpfner M: Anticancer properties of chimeric HDAC and kinase inhibitors. Semin Cancer Biol. Nov 12–2020.Epub ahead of print. View Article : Google Scholar : PubMed/NCBI

12 

Park SY and Kim JS: A short guide to histone deacetylases including recent progress on class II enzymes. Exp Mol Med. 52:204–212. 2020. View Article : Google Scholar : PubMed/NCBI

13 

Kaletsch A, Pinkerneil M, Hoffmann MJ, Jaguva Vasudevan AA, Wang C, Hansen FK, Wiek C, Hanenberg H, Gertzen C, Gohlke H, et al: Effects of novel HDAC inhibitors on urothelial carcinoma cells. Clin Epigenetics. 10:1002018. View Article : Google Scholar : PubMed/NCBI

14 

Gong D, Zeng Z, Yi F and Wu J: Inhibition of histone deacetylase 11 promotes human liver cancer cell apoptosis. Am J Transl Res. 11:983–990. 2019.PubMed/NCBI

15 

Steinemann G, Dittmer A, Kuzyniak W, Hoffmann B, Schrader M, Schobert R, Biersack B, Nitzsche B and Höpfner M: Animacroxam, a novel dual-mode compound targeting histone deacetylases and cytoskeletal integrity of testicular germ cell cancer cells. Mol Cancer Ther. 16:2364–2374. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Manal M, Chandrasekar MJN, Gomathi Priya J and Nanjan MJ: Inhibitors of histone deacetylase as antitumor agents: A critical review. Bioorg Chem. 67:18–42. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Juan LJ, Shia WJ, Chen MH, Yang WM, Seto E, Lin YS and Wu CW: Histone deacetylases specifically down-regulate p53-dependent gene activation. J Biol Chem. 275:20436–20443. 2000. View Article : Google Scholar : PubMed/NCBI

18 

Mann BS, Johnson JR, Cohen MH, Justice R and Pazdur R: FDA approval summary: Vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist. 12:1247–1252. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Streubel G, Schrepfer S, Kallus H, Parnitzke U, Wulff T, Hermann F, Borgmann M and Hamm S: Histone deacetylase inhibitor resminostat in combination with sorafenib counteracts platelet-mediated protumoral effects in hepatocellular carcinoma. Sci Rep. 11:95872021. View Article : Google Scholar

20 

Schmitt F, Gosch LC, Dittmer A, Rothemund M, Mueller T, Schobert R, Biersack B, Volkamer A and Höpfner M: Oxazole-bridged combretastatin A-4 derivatives with tethered hydroxamic acids: Structure-activity relations of new inhibitors of HDAC and/or tubulin function. Int J Mol Sci. 20:3832019. View Article : Google Scholar

21 

Méndez-Callejas GM, Leone S, Tanzarella C and Antoccia A: Combretastatin A-4 induces p53 mitochondrial-relocalisation independent-apoptosis in non-small lung cancer cells. Cell Biol Int. 38:296–308. 2014. View Article : Google Scholar

22 

Kim JH, Yoon EK, Chung HJ, Park SY, Hong KM, Lee CH, Lee YS, Choi K, Yang Y, Kim K and Kim IH: p53 acetylation enhances Taxol-induced apoptosis in human cancer cells. Apoptosis. 18:110–120. 2013. View Article : Google Scholar

23 

Tron GC, Pirali T, Sorba G, Pagliai F, Busacca S and Genazzani AA: Medicinal chemistry of combretastatin A4: present and future directions. J Med Chem. 49:3033–3044. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Hesham HM, Lasheen DS and Abouzid KAM: Chimeric HDAC inhibitors: Comprehensive review on the HDAC-based strategies developed to combat cancer. Med Res Rev. 38:2058–2109. 2018. View Article : Google Scholar : PubMed/NCBI

25 

Griggs J, Metcalfe JC and Hesketh R: Targeting tumour vasculature: The development of combretastatin A4. Lancet Oncol. 2:82–87. 2001. View Article : Google Scholar

26 

Gaspari R, Prota AE, Bargsten K, Cavalli A and Steinmetz MO: Structural basis of cis-and trans-combretastatin binding to tubulin. Chem. 2:102–113. 2017. View Article : Google Scholar

27 

Schaller E, Ma A, Gosch LC, Klefenz A, Schaller D, Goehringer N, Kaps L, Schuppan D, Volkamer A, Schobert R, et al: New 3-Aryl-2-(2-thienyl)acrylonitriles with high activity against hepatoma cells. Int J Mol Sci. 22:22432021. View Article : Google Scholar : PubMed/NCBI

28 

Nwosu ZC, Battello N, Rothley M, Piorońska W, Sitek B, Ebert MP, Hofmann U, Sleeman J, Wölfl S, Meyer C, et al: Liver cancer cell lines distinctly mimic the metabolic gene expression pattern of the corresponding human tumours. J Exp Clin Cancer Res. 37:2112018. View Article : Google Scholar : PubMed/NCBI

29 

Kasai F, Hirayama N, Ozawa M, Satoh M and Kohara A: HuH-7 reference genome profile: Complex karyotype composed of massive loss of heterozygosity. Hum Cell. 31:261–267. 2018. View Article : Google Scholar : PubMed/NCBI

30 

Nakabayashi H, Taketa K, Miyano K, Yamane T and Sato J: Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer Res. 42:3858–3863. 1982.PubMed/NCBI

31 

Monteil M, Migianu-Griffoni E, Sainte-Catherine O, Di Benedetto M and Lecouvey M: Bisphosphonate prodrugs: Synthesis and biological evaluation in HuH7 hepatocarcinoma cells. Eur J Med Chem. 77:56–64. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Xu L, Hausmann M, Dietmaier W, Kellermeier S, Pesch T, Stieber-Gunckel M, Lippert E, Klebl F and Rogler G: Expression of growth factor receptors and targeting of EGFR in cholangio-carcinoma cell lines. BMC Cancer. 10:3022010. View Article : Google Scholar

33 

Jo JR, An S, Ghosh S, Nedumaran B and Kim YD: Growth hormone promotes hepatic gluconeogenesis by enhancing BTG2-YY1 signaling pathway. Sci Rep. 11:189992021. View Article : Google Scholar : PubMed/NCBI

34 

Kuete V, Sandjo LP, Ouete JLN, Fouotsa H, Wiench B and Efferth T: Cytotoxicity and modes of action of three naturally occurring xanthones (8-hydroxycudraxanthone G, morusignin I and cudraxanthone I) against sensitive and multidrug-resistant cancer cell lines. Phytomedicine. 21:315–322. 2014. View Article : Google Scholar

35 

Gillies RJ, Didier N and Denton M: Determination of cell number in monolayer cultures. Anal Biochem. 159:109–113. 1986. View Article : Google Scholar : PubMed/NCBI

36 

Korzeniewski C and Callewaert DM: An enzyme-release assay for natural cytotoxicity. J Immunol Methods. 64:313–320. 1983. View Article : Google Scholar : PubMed/NCBI

37 

Nitzsche B, Gloesenkamp C, Schrader M, Ocker M, Preissner R, Lein M, Zakrzewicz A, Hoffmann B and Höpfner M: Novel compounds with antiangiogenic and antiproliferative potency for growth control of testicular germ cell tumours. Br J Cancer. 103:18–28. 2010. View Article : Google Scholar : PubMed/NCBI

38 

Sivandzade F, Bhalerao A and Cucullo L: Analysis of the mito-chondrial membrane potential using the cationic JC-1 dye as a sensitive fluorescent probe. Bio Protoc. 9:e31282019. View Article : Google Scholar

39 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

40 

Bobadilla AV, Arévalo J, Sarró E, Byrne HM, Maini PK, Carraro T, Balocco S, Meseguer A and Alarcón T: In vitro cell migration quantification method for scratch assays. J R Soc Interface. 16:201807092019. View Article : Google Scholar : PubMed/NCBI

41 

Almeida VM, Bezerra MA Jr, Nascimento JC and Amorim LMF: Anticancer drug screening: Standardization of in vitro wound healing assay. J Bras Patol Med Lab. 55:606–619. 2019. View Article : Google Scholar

42 

Serbedzija GN, Flynn E and Willett CE: Zebrafish angiogenesis: A new model for drug screening. Angiogenesis. 3:353–359. 1999. View Article : Google Scholar

43 

Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI

44 

Thorens B: GLUT2, glucose sensing and glucose homeostasis. Diabetologia. 58:221–232. 2015. View Article : Google Scholar

45 

Kaufmann SH and Earnshaw WC: Induction of apoptosis by cancer chemotherapy. Exp Cell Res. 256:42–49. 2000. View Article : Google Scholar : PubMed/NCBI

46 

Reers M, Smiley ST, Mottola-Hartshorn C, Chen A, Lin M and Chen LB: Mitochondrial membrane potential monitored by JC-1 dye. Methods Enzymol. 260:406–417. 1995. View Article : Google Scholar : PubMed/NCBI

47 

Kim R, Emi M and Tanabe K: Role of mitochondria as the gardens of cell death. Cancer Chemother Pharmacol. 57:545–553. 2006. View Article : Google Scholar

48 

Fridman JS and Lowe SW: Control of apoptosis by p53. Oncogene. 22:9030–9040. 2003. View Article : Google Scholar : PubMed/NCBI

49 

Kim R, Tanabe K, Uchida Y, Emi M, Inoue H and Toge T: Current status of the molecular mechanisms of anticancer drug-induced apoptosis. The contribution of molecular-level analysis to cancer chemotherapy. Cancer Chemother Pharmacol. 50:343–352. 2002. View Article : Google Scholar : PubMed/NCBI

50 

Giaginis C, Damaskos C, Koutsounas I, Zizi-Serbetzoglou A, Tsoukalas N, Patsouris E, Kouraklis G and Theocharis S: Histone deacetylase (HDAC)-1, -2, -4 and -6 expression in human pancreatic adenocarcinoma: Associations with clinicopathological parameters, tumor proliferative capacity and patients' survival. BMC Gastroenterol. 15:1482015. View Article : Google Scholar : PubMed/NCBI

51 

Garmpis N, Damaskos C, Garmpi A, Georgakopoulou VE, Sarantis P, Antoniou EA, Karamouzis MV, Nonni A, Schizas D, Diamantis E, et al: Histone deacetylase inhibitors in the treatment of hepatocellular carcinoma: Current evidence and future opportunities. J Pers Med. 11:2232021. View Article : Google Scholar : PubMed/NCBI

52 

Scholzen T and Gerdes J: The Ki-67 protein: From the known and the unknown. J Cell Physiol. 182:311–322. 2000. View Article : Google Scholar : PubMed/NCBI

53 

Kim HR, Rahman FU, Kim KS, Kim EK, Cho SM, Lee K, Moon OS, Seo YW, Yoon WK, Won YS, et al: Critical roles of E2F3 in growth and musculo-skeletal phenotype in mice. Int J Med Sci. 16:1557–1563. 2019. View Article : Google Scholar : PubMed/NCBI

54 

Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF and Yao TP: HDAC6 is a microtubule-associated deacetylase. Nature. 417:455–458. 2002. View Article : Google Scholar : PubMed/NCBI

55 

Garcin C and Straube A: Microtubules in cell migration. Essays Biochem. 63:509–520. 2019. View Article : Google Scholar : PubMed/NCBI

56 

Schaks M, Giannone G and Rottner K: Actin dynamics in cell migration. Essays Biochem. 63:483–495. 2019. View Article : Google Scholar : PubMed/NCBI

57 

Norouzzadeh M, Kalikias Y, Mohammadpour Z, Sharifi L and Mahmoudi M: Determining population doubling time and the appropriate number of HepG2 cells for culturing in 6-well plate. IJSBAR. 10:299–303. 2016.

58 

Deng B, Luo Q, Halim A, Liu Q, Zhang B and Song G: The antiangiogenesis role of histone deacetylase inhibitors: Their potential application to tumor therapy and tissue repair. DNA Cell Biol. 39:167–176. 2020. View Article : Google Scholar

59 

Tomaszewska B, Muzolf M, Grabysa R and Bodnar L: Cardiotoxicity of antiangiogenic drugs: Causes and mechanisms. OncoReview. 11:12–18. 2021. View Article : Google Scholar

60 

Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, Mori T, Nishimori H, Tamai K, Tokino T, Nakamura Y and Taya Y: p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell. 102:849–862. 2000. View Article : Google Scholar : PubMed/NCBI

61 

Matsuda K, Yoshida K, Taya Y, Nakamura K, Nakamura Y and Arakawa H: p53AIP1 regulates the mitochondrial apoptotic pathway. Cancer Res. 62:2883–2889. 2002.PubMed/NCBI

62 

Porter AG and Jänicke RU: Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 6:99–104. 1999. View Article : Google Scholar : PubMed/NCBI

63 

Lee YR and Park SY: P53 expression in hepatocellular carcinoma: Influence on the radiotherapeutic response of the hepatocellular carcinoma. Clin Mol Hepatol. 21:230–231. 2015. View Article : Google Scholar : PubMed/NCBI

64 

Li T, Zhang C, Hassan S, Liu X, Song F, Chen K, Zhang W and Yang J: Histone deacetylase 6 in cancer. J Hematol Oncol. 11:1112018. View Article : Google Scholar : PubMed/NCBI

65 

Aldana-Masangkay GI and Sakamoto KM: The role of HDAC6 in cancer. J Biomed Biotechnol. 2011:8758242011. View Article : Google Scholar

66 

Gao Y, Hubbert CC, Lu J, Lee YS, Lee JY and Yao TP: Histone deacetylase 6 regulates growth factor-induced actin remodeling and endocytosis. Mol Cell Biol. 27:8637–8647. 2007. View Article : Google Scholar : PubMed/NCBI

67 

Tran AD-A, Marmo TP, Salam AA, Che S, Finkelstein E, Kabarriti R, Xenias HS, Mazitschek R, Hubbert C, Kawaguchi Y, et al: HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions. J Cell Sci. 120:1469–1479. 2007. View Article : Google Scholar : PubMed/NCBI

68 

Enomoto T: Microtubule disruption induces the formation of actin stress fibers and focal adhesions in cultured cells: Possible involvement of the rho signal cascade. Cell Struct Funct. 21:317–326. 1996. View Article : Google Scholar : PubMed/NCBI

69 

Liu BP, Chrzanowska-Wodnicka M and Burridge K: Microtubule depolymerization induces stress fibers, focal adhesions, and DNA synthesis via the GTP-binding protein Rho. Cell Adhes Commun. 5:249–255. 1998. View Article : Google Scholar : PubMed/NCBI

70 

Zhang C, Willett C and Fremgen T: Zebrafish: An animal model for toxicological studies. Curr Protoc Toxicol. 17:1.7.1–1.7. 2003.

71 

Deroanne CF, Bonjean K, Servotte S, Devy L, Colige A, Clausse N, Blacher S, Verdin E, Foidart JM, Nusgens BV and Castronovo V: Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene. 21:427–436. 2002. View Article : Google Scholar : PubMed/NCBI

72 

Su M, Huang J, Liu S, Xiao Y, Qin X, Liu J, Pi C, Luo T, Li J, Chen X and Luo Z: The anti-angiogenic effect and novel mechanisms of action of Combretastatin A-4. Sci Rep. 6:281392016. View Article : Google Scholar : PubMed/NCBI

73 

Zhou J, Cheng M, Wu M, Boriboun C, Jujo K, Xu S, Zhao TC, Tang YL, Kishore R and Qin G: Contrasting roles of E2F2 and E2F3 in endothelial cell growth and ischemic angiogenesis. J Mol Cell Cardiol. 60:68–71. 2013. View Article : Google Scholar : PubMed/NCBI

74 

Heo YA and Syed YY: Regorafenib: A review in hepatocellular carcinoma. Drugs. 78:951–958. 2018. View Article : Google Scholar : PubMed/NCBI

75 

Labeur TA, Hofsink Q, Takkenberg RB, van Delden OM, Mathôt RAA, Schinner R, Malfertheiner P, Amthauer H, Schütte K, Basu B, et al: The value of sorafenib trough levels in patients with advanced hepatocellular carcinoma-a substudy of the SORAMIC trial. Acta Oncol. 59:1028–1035. 2020. View Article : Google Scholar : PubMed/NCBI

76 

Yuan H, Li AJ, Ma SL, Cui LJ, Wu B, Yin L and Wu MC: Inhibition of autophagy significantly enhances combination therapy with sorafenib and HDAC inhibitors for human hepa-toma cells. World J Gastroenterol. 20:4953–4962. 2014. View Article : Google Scholar : PubMed/NCBI

77 

Bitzer M, Horger M, Giannini EG, Ganten TM, Wörns MA, Siveke JT, Dollinger MM, Gerken G, Scheulen ME, Wege H, et al: Resminostat plus sorafenib as second-line therapy of advanced hepatocellular carcinoma-The SHELTER study. J Hepatol. 65:280–288. 2016. View Article : Google Scholar : PubMed/NCBI

78 

Freese K, Seitz T, Dietrich P, Lee SML, Thasler WE, Bosserhoff A and Hellerbrand C: Histone deacetylase expressions in hepato-cellular carcinoma and functional effects of histone deacetylase inhibitors on liver cancer cells in vitro. Cancers (Basel). 11:15872019. View Article : Google Scholar

79 

Gordon SW, McGuire WP III, Shafer DA, Sterling RK, Lee HM, Matherly SC, Roberts JD, Bose P, Tombes MB, Shrader EE, et al: Phase I study of sorafenib and vorinostat in advanced hepatocellular carcinoma. Am J Clin Oncol. 42:649–654. 2019. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Bär SI, Dittmer A, Nitzsche B, Ter-Avetisyan G, Fähling M, Klefenz A, Kaps L, Biersack B, Schobert R, Höpfner M, Höpfner M, et al: Chimeric HDAC and the cytoskeleton inhibitor broxbam as a novel therapeutic strategy for liver cancer. Int J Oncol 60: 73, 2022.
APA
Bär, S.I., Dittmer, A., Nitzsche, B., Ter-Avetisyan, G., Fähling, M., Klefenz, A. ... Höpfner, M. (2022). Chimeric HDAC and the cytoskeleton inhibitor broxbam as a novel therapeutic strategy for liver cancer. International Journal of Oncology, 60, 73. https://doi.org/10.3892/ijo.2022.5363
MLA
Bär, S. I., Dittmer, A., Nitzsche, B., Ter-Avetisyan, G., Fähling, M., Klefenz, A., Kaps, L., Biersack, B., Schobert, R., Höpfner, M."Chimeric HDAC and the cytoskeleton inhibitor broxbam as a novel therapeutic strategy for liver cancer". International Journal of Oncology 60.6 (2022): 73.
Chicago
Bär, S. I., Dittmer, A., Nitzsche, B., Ter-Avetisyan, G., Fähling, M., Klefenz, A., Kaps, L., Biersack, B., Schobert, R., Höpfner, M."Chimeric HDAC and the cytoskeleton inhibitor broxbam as a novel therapeutic strategy for liver cancer". International Journal of Oncology 60, no. 6 (2022): 73. https://doi.org/10.3892/ijo.2022.5363
Copy and paste a formatted citation
x
Spandidos Publications style
Bär SI, Dittmer A, Nitzsche B, Ter-Avetisyan G, Fähling M, Klefenz A, Kaps L, Biersack B, Schobert R, Höpfner M, Höpfner M, et al: Chimeric HDAC and the cytoskeleton inhibitor broxbam as a novel therapeutic strategy for liver cancer. Int J Oncol 60: 73, 2022.
APA
Bär, S.I., Dittmer, A., Nitzsche, B., Ter-Avetisyan, G., Fähling, M., Klefenz, A. ... Höpfner, M. (2022). Chimeric HDAC and the cytoskeleton inhibitor broxbam as a novel therapeutic strategy for liver cancer. International Journal of Oncology, 60, 73. https://doi.org/10.3892/ijo.2022.5363
MLA
Bär, S. I., Dittmer, A., Nitzsche, B., Ter-Avetisyan, G., Fähling, M., Klefenz, A., Kaps, L., Biersack, B., Schobert, R., Höpfner, M."Chimeric HDAC and the cytoskeleton inhibitor broxbam as a novel therapeutic strategy for liver cancer". International Journal of Oncology 60.6 (2022): 73.
Chicago
Bär, S. I., Dittmer, A., Nitzsche, B., Ter-Avetisyan, G., Fähling, M., Klefenz, A., Kaps, L., Biersack, B., Schobert, R., Höpfner, M."Chimeric HDAC and the cytoskeleton inhibitor broxbam as a novel therapeutic strategy for liver cancer". International Journal of Oncology 60, no. 6 (2022): 73. https://doi.org/10.3892/ijo.2022.5363
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team