Megadoses of Ascorbate as a New Chemotherapeutic Approach in Uveal Melanoma: A Preliminary In Vitro Investigation
|Domenico Mastrangelo1*, Lauretta Massai1, Klara Valyi-Nagy2, Michela Muscettola1, Margherita Aglianò1, Leda Lodi1, Francesco Di Pisa1 and Giovanni Grasso1|
|1Dipartimento di Scienze Mediche, Chirurgiche e Neuroscienze, Università di Siena, Italy|
|2Department of Pathology, University of Illinois, Chicago, USA|
|Corresponding Author :||Domenico Mastrangelo, MD
Senior Scientist (Research)
Dipartimento di Scienze Mediche
Chirurgiche e Neuroscienze, University of Siena
Polo Scientifico S. Miniato, 53100, Siena, Italy
Tel: 0039 0577 3691010
Fax: 0039 0577 369185
E-mail: [email protected]
|Received October 16, 2013; Accepted December 13, 2013; Published December 21, 2013|
|Citation: Mastrangelo D, Massai L, Valyi-Nagy K, Muscettola M, Aglianò M, et al. (2013) Megadoses of Ascorbate as a New Chemotherapeutic Approach in Uveal Melanoma: A Preliminary In Vitro Investigation. J Clin Exp Ophthalmol 4:315. doi:10.4172/2155-9570.1000315|
|Copyright: © 2013 Mastrangelo D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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Background: Despite the more recent advances, there is still no effective systemic therapy for Uveal Melanoma (UM). However, a better understanding of the role of oxidative stress in cancer, has more recently led to a completely new approach to the systemic therapy of cancer, and modulators of the oxidative balance, such as sodium ascorbate (ASC) or arsenic trioxide (ATO), have already entered advanced phases of preclinical and clinical development.
Since high doses of ASC have already demonstrated a strong cytotoxic effect on different human cancer cell lines, we have undertaken the present investigation in order to test the sensitivity of OCM1 and C918 uveal melanoma (UM) cell lines to high doses of ASC, in vitro, as compared to ATO, a pro-oxidant drug which has already undergone extensive in vitro and pre-clinical investigation in UM.
Methods: Both OCM1 and C918 UM cell lines have been exposed to increasing doses of either ASC or ATO, to build a dose-response curve around the peak plasma concentrations reached by both chemicals. The assessment of cell count and viability was performed with flow cytometry.
Results: Both OCM1 and C918 UM cell lines are highly sensitive to ASC in the range of millimolar (mM) concentrations which can be usually reached by the intravenous injection of high doses of the compound. ATO at the dosages used in this study, never reached the LC50. When the exposure to ASC was reduced to two hours, it still had significant effects on survival of both OCM1 and C918 UM cells.
Conclusions: This report shows that ASC is highly cytotoxic for both OCM1 and C918 UM cells, when used in high, pro-oxidant doses. To our knowledge, this is the first report showing that UM cells can be efficiently killed, in vitro, with high doses of ASC.