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
November-2019 Volume 55 Issue 5

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
November-2019 Volume 55 Issue 5

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_Data.pdf
Article Open Access

Selective uveal melanoma inhibition with calcium channel blockade

  • Authors:
    • Michael Shaughnessy
    • Grace Lamuraglia
    • Nikolai Klebanov
    • Zhenyu Ji
    • Anpuchchelvi Rajadurai
    • Raj Kumar
    • Keith Flaherty
    • Hensin Tsao
  • View Affiliations / Copyright

    Affiliations: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114-2605, USA, Department of Medicine, Division of Medical Oncology, Massachusetts General Hospital Cancer Center, Center for Melanoma, Harvard Medical School, Boston, MA 02114-2605, USA
    Copyright: © Shaughnessy et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1090-1096
    |
    Published online on: September 6, 2019
       https://doi.org/10.3892/ijo.2019.4873
  • 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

Uveal malignant melanoma (UMM), the most common primary adult intraocular tumor with a marked metastatic potential, is genetically unique and has unfortunately had few treatment breakthroughs. In this study, we subjected a UMM cell line to high‑throughput library screening with 1,018 FDA‑approved compounds to identify potential UMM‑selective cytotoxic agents. Amlodipine, a dihydropyridine calcium channel blocker (CCB), ranked no. 2 and no. 8 of the most cytotoxic compounds. Thus, we further characterized the differential effects of calcium blockade on UMM and cutaneous malignant melanoma (CMM) lines in vitro using growth inhibition, cell cycle progression, apoptosis and senescence assays. Amlodipine had a significantly higher growth inhibitory potency in UMM (IC50=13.1 µM) than CMM (IC50=15.9 µM, P<0.05) lines. In 3D spherical cell culture, amlodipine treatment significantly impaired tissue volume growth in two UMM lines, but exerted no significant effects among all 3 CMM lines tested. Treatment with 10 and 20 µM amlodipine induced a significant impairment of cell cycle progression and the apoptosis of UMM lines, implicating both of these processes as mediators of the observed growth inhibition in UMM compared to CMM. On the whole, the findings of this study suggest that calcium channel blockade is a potentially effective strategy for selective uveal melanoma targeting.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Shields CL, Furuta M, Thangappan A, Nagori S, Mashayekhi A, Lally DR, Kelly CC, Rudich DS, Nagori AV, Wakade OA, et al: Metastasis of uveal melanoma millimeter-by-millimeter in 8033 consecutive eyes. Arch Ophthalmol. 127:989–998. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Chattopadhyay C, Kim DW, Gombos DS, Oba J, Qin Y, Williams MD, Esmaeli B, Grimm EA, Wargo JA, Woodman SE, et al: Uveal melanoma: From diagnosis to treatment and the science in between. Cancer. 122:2299–2312. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Shaughnessy M, Klebanov N and Tsao H: Clinical and therapeutic implications of melanoma genomics. J Transl Genet Genom. 2:142018.

4 

Singh AD and Topham A: Incidence of uveal melanoma in the United States: 1973-1997. Ophthalmology. 110:956–961. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Kaliki S and Shields CL: Uveal melanoma: Relatively rare but deadly cancer. Eye (Lond). 31:241–257. 2017. View Article : Google Scholar

6 

Grisanti S and Tura A: Uveal melanoma. Noncutaneous melanoma. Scott JF and Gerstenblith MR: Codon Publications; Brisbane: 2018, View Article : Google Scholar

7 

Eskelin S, Pyrhönen S, Hahka-Kemppinen M, Tuomaala S and Kivelä T: A prognostic model and staging for metastatic uveal melanoma. Cancer. 97:465–475. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Field MG, Durante MA, Anbunathan H, Cai LZ, Decatur CL, Bowcock AM, Kurtenbach S and Harbour JW: Punctuated evolution of canonical genomic aberrations in uveal melanoma. Nat Commun. 9:1162018. View Article : Google Scholar : PubMed/NCBI

9 

Augsburger JJ, Corrêa ZM and Shaikh AH: Effectiveness of treatments for metastatic uveal melanoma. Am J Ophthalmol. 148:119–127. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Desjardins L, Levy C, Lumbroso Le Rouic L, Cassoux N, Piperno-Neumann S, Mariani P, Servois V, Dendale R, Plancher C and Asselain B: Adjuvant intravenous therapy by fotemustine in uveal melanoma: A randomised study. Acta Ophthalmologica. Sep 15–2011.Epub ahead of print. View Article : Google Scholar

11 

Komatsubara KM and Carvajal RD: Immunotherapy for the treatment of uveal melanoma: Current status and emerging therapies. Curr Oncol Rep. 19:452017. View Article : Google Scholar : PubMed/NCBI

12 

Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S, Cekic S and Stefanovic V: Ocular melanoma: An overview of the current status. Int J Clin Exp Pathol. 6:1230–1244. 2013.PubMed/NCBI

13 

Stewart TA, Yapa KT and Monteith GR: Altered calcium signaling in cancer cells. Biochim Biophys Acta. 1848:2502–2511. 2015. View Article : Google Scholar

14 

Brzozowski JS and Skelding KA: The multi-functional calcium/calmodulin stimulated protein kinase (CaMK) family: Emerging targets for anti-cancer therapeutic intervention. Pharmaceuticals (Basel). 12. pp. 122019, View Article : Google Scholar

15 

Cui C, Merritt R, Fu L and Pan Z: Targeting calcium signaling in cancer therapy. Acta Pharm Sin B. 7:3–17. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Wang X, Liu H, Xu Y, Xie J, Zhu D, Amos CI, Fang S, Lee JE, Li X, Nan H, et al: Genetic variants in the calcium signaling pathway genes are associated with cutaneous melanoma-specific survival. Carcinogenesis. 40:279–288. 2019. View Article : Google Scholar : PubMed/NCBI

17 

Nussinov R, Wang G, Tsai CJ, Jang H, Lu S, Banerjee A, Zhang J and Gaponenko V: Calmodulin and PI3K signaling in KRAS cancers. Trends Cancer. 3:214–224. 2017. View Article : Google Scholar : PubMed/NCBI

18 

Maiques O, Barceló C, Panosa A, Pijuan J, Orgaz JL, Rodriguez-Hernandez I, Matas-Nadal C, Tell G, Vilella R, Fabra A, et al: T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1. Pigment Cell Melanoma Res. 31:484–495. 2018. View Article : Google Scholar : PubMed/NCBI

19 

Umemura M, Baljinnyam E, Feske S, De Lorenzo MS, Xie LH, Feng X, Oda K, Makino A, Fujita T, Yokoyama U, et al: Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration. PLoS One. 9:e892922014. View Article : Google Scholar

20 

Chen X, Wu Q, Depeille P, Chen P, Thornton S, Kalirai H, Coupland SE, Roose JP and Bastian BC: RasGRP3 mediates MAPK pathway activation in GNAQ mutant uveal melanoma. Cancer Cell. 31:685–696.e6. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Xie S, Naslavsky N and Caplan S: Diacylglycerol kinases in membrane trafficking. Cell Logist. 5:e1078431. 2015. View Article : Google Scholar

22 

Opie LH: Pharmacological differences between calcium antagonists. Eur Heart J. 18(Suppl A): A71–A79. 1997. View Article : Google Scholar : PubMed/NCBI

23 

Das A, Pushparaj C, Bahí N, Sorolla A, Herreros J, Pamplona R, Vilella R, Matias-Guiu X, Martí RM and Cantí C: Functional expression of voltage-gated calcium channels in human melanoma. Pigment Cell Melanoma Res. 25:200–212. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Striessnig J, Ortner NJ and Pinggera A: Pharmacology of L-type calcium channels: Novel drugs for old targets? Curr Mol Pharmacol. 8:110–122. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Zou J, Li Y, Fan HQ and Wang JG: Effects of dihydropyridine calcium channel blockers on oxidized low-density lipoprotein induced proliferation and oxidative stress of vascular smooth muscle cells. BMC Res Notes. 5:1682012. View Article : Google Scholar : PubMed/NCBI

26 

Lee H, Kang S and Kim W: Drug repositioning for cancer therapy based on large-scale drug-induced transcriptional signatures. PLoS One. 11:e01504602016. View Article : Google Scholar : PubMed/NCBI

27 

Ohba T, Watanabe H, Murakami M, Radovanovic M, Iino K, Ishida M, Tosa S, Ono K and Ito H: Amlodipine inhibits cell proliferation via PKD1-related pathway. Biochem Biophys Res Commun. 369:376–381. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Shaughnessy M, Lamuraglia G, Klebanov N, Ji Z, Rajadurai A, Kumar R, Flaherty K and Tsao H: Selective uveal melanoma inhibition with calcium channel blockade. Int J Oncol 55: 1090-1096, 2019.
APA
Shaughnessy, M., Lamuraglia, G., Klebanov, N., Ji, Z., Rajadurai, A., Kumar, R. ... Tsao, H. (2019). Selective uveal melanoma inhibition with calcium channel blockade. International Journal of Oncology, 55, 1090-1096. https://doi.org/10.3892/ijo.2019.4873
MLA
Shaughnessy, M., Lamuraglia, G., Klebanov, N., Ji, Z., Rajadurai, A., Kumar, R., Flaherty, K., Tsao, H."Selective uveal melanoma inhibition with calcium channel blockade". International Journal of Oncology 55.5 (2019): 1090-1096.
Chicago
Shaughnessy, M., Lamuraglia, G., Klebanov, N., Ji, Z., Rajadurai, A., Kumar, R., Flaherty, K., Tsao, H."Selective uveal melanoma inhibition with calcium channel blockade". International Journal of Oncology 55, no. 5 (2019): 1090-1096. https://doi.org/10.3892/ijo.2019.4873
Copy and paste a formatted citation
x
Spandidos Publications style
Shaughnessy M, Lamuraglia G, Klebanov N, Ji Z, Rajadurai A, Kumar R, Flaherty K and Tsao H: Selective uveal melanoma inhibition with calcium channel blockade. Int J Oncol 55: 1090-1096, 2019.
APA
Shaughnessy, M., Lamuraglia, G., Klebanov, N., Ji, Z., Rajadurai, A., Kumar, R. ... Tsao, H. (2019). Selective uveal melanoma inhibition with calcium channel blockade. International Journal of Oncology, 55, 1090-1096. https://doi.org/10.3892/ijo.2019.4873
MLA
Shaughnessy, M., Lamuraglia, G., Klebanov, N., Ji, Z., Rajadurai, A., Kumar, R., Flaherty, K., Tsao, H."Selective uveal melanoma inhibition with calcium channel blockade". International Journal of Oncology 55.5 (2019): 1090-1096.
Chicago
Shaughnessy, M., Lamuraglia, G., Klebanov, N., Ji, Z., Rajadurai, A., Kumar, R., Flaherty, K., Tsao, H."Selective uveal melanoma inhibition with calcium channel blockade". International Journal of Oncology 55, no. 5 (2019): 1090-1096. https://doi.org/10.3892/ijo.2019.4873
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