In Vitro Effects of Histone Deacetylase Inhibitors and Mitomycin C on Tenon Capsule Fibroblasts and Conjunctival Melanoma Cells

Abstract

To investigate the effects of mitomycin C and the histone deacetylase inhibitors sodium butyrate and trichostatin on the viability and growth of conjunctival melanoma cell lines and Tenon capsule fibroblasts. Methods: Cells were treated with a range of concentrations of sodium butyrate, trichostatin, and mitomycin C. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide) assays were performed 48 hours after treatment. Treated cells were stained with acridine orange/ethidium bromide to assess for cell death. Cellcycle changes in histone deacetylase inhibitor-treated melanoma cells were quantified using flow cytometry. Results: All agents induced dose-dependent cell death in the melanoma cell lines; however, sodium butyrate and trichostatin were relatively nontoxic to Tenon capsule fibroblasts. Acridine orange/ethidium bromide staining indicated that sodium butyrate and trichostatin induced apoptotic cell death. At low doses, sodium butyrate and trichostatin induced a G1 cell-cycle block in the melanoma cells.

Chemosensitivity of conjunctival melanoma cell lines to single chemotherapeutic agents and combinations

“…One study that was performed on the same cell lines examined the efficacy of MMC in inhibiting conjunctival melanoma cell growth in vitro 17. Our in vitro data support the results and could add the IC 50 as additional information.…”

Evaluation of melanogenesis in A-375 melanoma cells treated with 5,7-dimethoxycoumarin and valproic acid

“…The function of HDACis is mainly associated with restoring the equilibrium between the acetylation and deacetylation of histones [41]. Many HDACis, among them VPA, are currently undergoing phase I or II clinical trials [11,41].…”

“…Many HDACis, among them VPA, are currently undergoing phase I or II clinical trials [11,41]. Daud et al [42] used VPA (30-90 mg/kg/24 h) and the topoisomerase I inhibitor Karenitecin (KNT at 0.8 and 1 mg/m 2 /24 h) and achieved stabilization of the disease in 13 out of 33 (39%) patients with the diagnosed melanoma.…”

Conjunctival melanoma: pitfalls and dilemmas in management

“…Single cases of more severe complications including an intumescent cataract or a corneal decompensation requiring an ocular surface prosthesis have been reported [36,37]. Other topical adjuvant agents with better tolerability are being explored [38]. There is a recent report with encouraging results of conjunctival melanoma regression following the use of topical Interferon alfa2b in patients intolerant of mitomycin C or with recurrence despite prior topical chemotherapy [39].…”