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
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
February-2017 Volume 37 Issue 2

Full Size Image

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
February-2017 Volume 37 Issue 2

Full Size Image

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
Article

Escin induces apoptosis in human renal cancer cells through G2/M arrest and reactive oxygen species-modulated mitochondrial pathways

  • Authors:
    • Sheau-Yun Yuan
    • Chen-Li Cheng
    • Shian-Shiang Wang
    • Hao-Chung Ho
    • Kun-Yuan Chiu
    • Chuan-Shu Chen
    • Cheng-Che Chen
    • Ming-Yuh Shiau
    • Yen-Chuan Ou
  • View Affiliations / Copyright

    Affiliations: Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung 40705, Taiwan, R.O.C., Department of Nursing, Hung Kuang University, Taichung 43302, Taiwan, R.O.C.
  • Pages: 1002-1010
    |
    Published online on: January 3, 2017
       https://doi.org/10.3892/or.2017.5348
  • 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

Escin, a natural pentacyclic triterpenoid compound, exhibits antitumor effects on various types of human cancer cells, but its effect on human renal cancer cells has not been fully elucidated. In the present study, we demonstrated that escin elicits cytotoxic effects on human renal cancer cells (786-O and Caki-1) in a dose-dependent manner, as determined by MTT assay. Escin induced G2/M arrest, and then increased the sub-G1 population, Annexin V binding, activation of caspase-9/-3, cleavage of poly(ADP-ribose) polymerase (PARP) and Bax protein. Escin also decreased the anti-apoptotic protein levels of Bcl-2, X-linked inhibitor of apoptosis protein and survivin. In addition, escin induced reactive oxygen species (ROS) generation, leading to mitochondrial membrane potential dysfunction and inducing apoptosis in 786-O renal cancer cells, which were suppressed by antioxidants, such as NAC. Collectively, our results suggest that escin induces apoptosis via the intrinsic-mitochondrial apoptosis pathway through G2/M arrest and ROS generation in human renal cancer cells. Escin appears to have potential as a clinically useful chemotherapeutic agent for human renal cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Znaor A, Lortet-Tieulent J, Laversanne M, Jemal A and Bray F: International variations and trends in renal cell carcinoma incidence and mortality. Eur Urol. 67:519–530. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Cheville JC, Lohse CM, Zincke H, Weaver AL and Blute ML: Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol. 27:612–624. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Singer EA, Gupta GN and Srinivasan R: Update on targeted therapies for clear cell renal cell carcinoma. Curr Opin Oncol. 23:283–289. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Janzen NK, Kim HL, Figlin RA and Belldegrun AS: Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am. 30:843–852. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Amato RJ: Chemotherapy for renal cell carcinoma. Semin Oncol. 27:177–186. 2000.PubMed/NCBI

6 

Hsu RJ, Ho JY, Cha TL, Yu DS, Wu CL, Huang WP, Chu P, Chen YH, Chen JT and Yu CP: WNT10A plays an oncogenic role in renal cell carcinoma by activating WNT/β-catenin pathway. PLoS One. 7:e476492012. View Article : Google Scholar : PubMed/NCBI

7 

Gurib-Fakim A: Medicinal plants: Traditions of yesterday and drugs of tomorrow. Mol Aspects Med. 27:1–93. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Cragg GM and Newman DJ: Natural products: A continuing source of novel drug leads. Biochim Biophys Acta. 1830:3670–3695. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Tutton PJ and Barkla DH: Influence of prostaglandin analogues on epithelial cell proliferation and xenograft growth. Br J Cancer. 41:47–51. 1980. View Article : Google Scholar : PubMed/NCBI

10 

Stone OJ: Cancer resistance, carcinogenesis and ground substance viscosity. Med Hypotheses. 20:117–124. 1986. View Article : Google Scholar : PubMed/NCBI

11 

Sirtori CR: Aescin: Pharmacology, pharmacokinetics and therapeutic profile. Pharmacol Res. 44:183–193. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Fu F, Hou Y, Jiang W, Wang R and Liu K: Escin: Inhibiting inflammation and promoting gastrointestinal transit to attenuate formation of postoperative adhesions. World J Surg. 29:1614–1620. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Diehm C, Trampisch HJ, Lange S and Schmidt C: Comparison of leg compression stocking and oral horse-chestnut seed extract therapy in patients with chronic venous insufficiency. Lancet. 347:292–294. 1996. View Article : Google Scholar : PubMed/NCBI

14 

Bielanski TE and Piotrowski ZH: Horse-chestnut seed extract for chronic venous insufficiency. J Fam Pract. 48:171–172. 1999.PubMed/NCBI

15 

Rothkopf M and Vogel G: New findings on the efficacy and mode of action of the horse chestnut saponin escin. Arzneimittelforschung. 26:225–235. 1976.(In German). PubMed/NCBI

16 

Matsuda H, Li Y, Murakami T, Ninomiya K, Yamahara J and Yoshikawa M: Effects of escins Ia, Ib, IIa, and IIb from horse chestnut, the seeds of Aesculus hippocastanum L., on acute inflammation in animals. Biol Pharm Bull. 20:1092–1095. 1997. View Article : Google Scholar : PubMed/NCBI

17 

Wang XH, Xu B, Liu JT and Cui JR: Effect of beta-escin sodium on endothelial cells proliferation, migration and apoptosis. Vascul Pharmacol. 49:158–165. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Kimura H, Ogawa S, Jisaka M, Kimura Y, Katsube T and Yokota K: Identification of novel saponins from edible seeds of Japanese horse chestnut (Aesculus turbinata BLUME) after treatment with wooden ashes and their nutraceutical activity. J Pharm Biomed Anal. 41:1657–1665. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Hu JN, Zhu XM, Han LK, Saito M, Sun YS, Yoshikawa M, Kimura Y and Zheng YN: Anti-obesity effects of escins extracted from the seeds of Aesculus turbinata BLUME (Hippocastanaceae). Chem Pharm Bull. 56:12–16. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Marhuenda E, Alarcón de la Lastra C and Martín MJ: Antisecretory and gastroprotective effects of aescine in rats. Gen Pharmacol. 25:1213–1219. 1994. View Article : Google Scholar : PubMed/NCBI

21 

Wang YW, Wang SJ, Zhou YN, Pan SH and Sun B: Escin augments the efficacy of gemcitabine through down-regulation of nuclear factor-κB and nuclear factor-κB-regulated gene products in pancreatic cancer both in vitro and in vivo. J Cancer Res Clin Oncol. 138:785–797. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Zhang Z, Gao J, Cai X, Zhao Y, Wang Y, Lu W, Gu Z, Zhang S and Cao P: Escin sodium induces apoptosis of human acute leukemia Jurkat T cells. Phytother Res. 25:1747–1755. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Niu YP, Wu LM, Jiang YL, Wang WX and Li LD: Beta-escin, a natural triterpenoid saponin from Chinese horse chestnut seeds, depresses HL-60 human leukaemia cell proliferation and induces apoptosis. J Pharm Pharmacol. 60:1213–1220. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Niu YP, Li LD and Wu LM: Beta-aescin: A potent natural inhibitor of proliferation and inducer of apoptosis in human chronic myeloid leukemia K562 cells in vitro. Leuk Lymphoma. 49:1384–1391. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Shen DY, Kang JH, Song W, Zhang WQ, Li WG, Zhao Y and Chen QX: Apoptosis of human cholangiocarcinoma cell lines induced by β-escin through mitochondrial caspase-dependent pathway. Phytother Res. 25:1519–1526. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Zhou XY, Fu FH, Li Z, Dong QJ, He J and Wang CH: Escin, a natural mixture of triterpene saponins, exhibits antitumor activity against hepatocellular carcinoma. Planta Med. 75:1580–1585. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Patlolla JM, Raju J, Swamy MV and Rao CV: β-Escin inhibits colonic aberrant crypt foci formation in rats and regulates the cell cycle growth by inducing p21waf1/cip1 in colon cancer cells. Mol Cancer Ther. 5:1459–1466. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Xia Z, Bergstrand A, DePierre JW and Nässberger L: The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 13:338–347. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Bindokas VP, Jordán J, Lee CC and Miller RJ: Superoxide production in rat hippocampal neurons: Selective imaging with hydroethidine. J Neurosci. 16:1324–1336. 1996.PubMed/NCBI

30 

Satoh T, Numakawa T, Abiru Y, Yamagata T, Ishikawa Y, Enokido Y and Hatanaka H: Production of reactive oxygen species and release of L-glutamate during superoxide anion-induced cell death of cerebellar granule neurons. J Neurochem. 70:316–324. 1998. View Article : Google Scholar : PubMed/NCBI

31 

Yuan SY, Cheng CL, Ho HC, Wang SS, Chiu KY, Su CK, Ou YC and Lin CC: Nortriptyline induces mitochondria and death receptor-mediated apoptosis in bladder cancer cells and inhibits bladder tumor growth in vivo. Eur J Pharmacol. 761:309–320. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Wyllie AH, Kerr JF and Currie AR: Cell death: The significance of apoptosis. Int Rev Cytol. 68:251–306. 1980. View Article : Google Scholar : PubMed/NCBI

33 

Brunelle JK and Letai A: Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci. 122:437–441. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Wu CS, Chen YJ, Chen JJ, Shieh JJ, Huang CH, Lin PS, Chang GC, Chang JT and Lin CC: Terpinen-4-ol induces apoptosis in human nonsmall cell lung cancer in vitro and in vivo. Evid Based Complement Alternat Med. 2012:8182612012. View Article : Google Scholar : PubMed/NCBI

35 

Cheng SB, Wu LC, Hsieh YC, Wu CH, Chan YJ, Chang LH, Chang CM, Hsu SL, Teng CL and Wu CC: Supercritical carbon dioxide extraction of aromatic turmerone from Curcuma longa Linn. induces apoptosis through reactive oxygen species-triggered intrinsic and extrinsic pathways in human hepatocellular carcinoma HepG2 cells. J Agric Food Chem. 60:9620–9630. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Simon HU, Haj-Yehia A and Levi-Schaffer F: Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis. 5:415–418. 2000. View Article : Google Scholar : PubMed/NCBI

37 

Piao S, Kang M, Lee YJ, Choi WS, Chun YS, Kwak C and Kim HH: Cytotoxic effects of escin on human castration-resistant prostate cancer cells through the induction of apoptosis and G2/M cell cycle arrest. Urology. 84:982.e1–982.e7. 2014. View Article : Google Scholar

38 

Rimmon A, Vexler A, Berkovich L, Earon G, Ron I and Lev-Ari S: Escin chemosensitizes human pancreatic cancer cells and inhibits the nuclear factor-kappaB signaling pathway. Biochem Res Int. 2013:2517522013. View Article : Google Scholar : PubMed/NCBI

39 

Küçükkurt I, Ince S, Keleş H, Akkol EK, Avci G, Yeşilada E and Bacak E: Beneficial effects of Aesculus hippocastanum L. seed extract on the body's own antioxidant defense system on subacute administration. J Ethnopharmacol. 129:18–22. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yuan S, Cheng C, Wang S, Ho H, Chiu K, Chen C, Chen C, Shiau M and Ou Y: Escin induces apoptosis in human renal cancer cells through G2/M arrest and reactive oxygen species-modulated mitochondrial pathways. Oncol Rep 37: 1002-1010, 2017.
APA
Yuan, S., Cheng, C., Wang, S., Ho, H., Chiu, K., Chen, C. ... Ou, Y. (2017). Escin induces apoptosis in human renal cancer cells through G2/M arrest and reactive oxygen species-modulated mitochondrial pathways. Oncology Reports, 37, 1002-1010. https://doi.org/10.3892/or.2017.5348
MLA
Yuan, S., Cheng, C., Wang, S., Ho, H., Chiu, K., Chen, C., Chen, C., Shiau, M., Ou, Y."Escin induces apoptosis in human renal cancer cells through G2/M arrest and reactive oxygen species-modulated mitochondrial pathways". Oncology Reports 37.2 (2017): 1002-1010.
Chicago
Yuan, S., Cheng, C., Wang, S., Ho, H., Chiu, K., Chen, C., Chen, C., Shiau, M., Ou, Y."Escin induces apoptosis in human renal cancer cells through G2/M arrest and reactive oxygen species-modulated mitochondrial pathways". Oncology Reports 37, no. 2 (2017): 1002-1010. https://doi.org/10.3892/or.2017.5348
Copy and paste a formatted citation
x
Spandidos Publications style
Yuan S, Cheng C, Wang S, Ho H, Chiu K, Chen C, Chen C, Shiau M and Ou Y: Escin induces apoptosis in human renal cancer cells through G2/M arrest and reactive oxygen species-modulated mitochondrial pathways. Oncol Rep 37: 1002-1010, 2017.
APA
Yuan, S., Cheng, C., Wang, S., Ho, H., Chiu, K., Chen, C. ... Ou, Y. (2017). Escin induces apoptosis in human renal cancer cells through G2/M arrest and reactive oxygen species-modulated mitochondrial pathways. Oncology Reports, 37, 1002-1010. https://doi.org/10.3892/or.2017.5348
MLA
Yuan, S., Cheng, C., Wang, S., Ho, H., Chiu, K., Chen, C., Chen, C., Shiau, M., Ou, Y."Escin induces apoptosis in human renal cancer cells through G2/M arrest and reactive oxygen species-modulated mitochondrial pathways". Oncology Reports 37.2 (2017): 1002-1010.
Chicago
Yuan, S., Cheng, C., Wang, S., Ho, H., Chiu, K., Chen, C., Chen, C., Shiau, M., Ou, Y."Escin induces apoptosis in human renal cancer cells through G2/M arrest and reactive oxygen species-modulated mitochondrial pathways". Oncology Reports 37, no. 2 (2017): 1002-1010. https://doi.org/10.3892/or.2017.5348
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