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

  • Published online on: September 6, 2019     https://doi.org/10.3892/ijo.2019.4873
  • Pages: 1090-1096
  • Copyright: © Shaughnessy et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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November-2019
Volume 55 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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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