%0 Journal Article
%T Inhibitory Effects of Trehalose on Malignant Melanoma Cell Growth: Implications for a Novel Topical Anticancer Agent on the Ocular Surface
%A Takashi Kudo
%A Kimio Takeuchi
%A Yu-ichi Ebina
%A Mitsuru Nakazawa
%J ISRN Ophthalmology
%D 2012
%R 10.5402/2012/968493
%X Purpose. To investigate the inhibitory effects of trehalose on malignant melanoma cell growth. Methods. We cultured human malignant melanoma cells in a medium containing trehalose (control/2.5%/5.0%/7.5%/10.0%) and used the MTT assay to evaluate the growth activities. Subsequently, trehalose was topically instilled on subconjunctivally inoculated melanoma cells in F334/NJcl-rmu/rmu rats, followed by a histopathological evaluation of tumor growth. Using flow cytometry, we compared the distribution of the cell cycle, rate of apoptotic cells, and intracellular factors related to the cell cycle in cultured melanoma cells after trehalose treatment. Results. The MTT study showed that proliferation of melanoma cells was significantly inhibited by ¨R£¿5% of trehalose concentrations in the culture media. Subconjunctivally inoculated melanoma cell masses were significantly smaller in eyes administered trehalose as compared to controls. Flow cytometry analyses demonstrated that the trehalose groups had increased rates of G2/M phase cells and apoptotic cells in the cell culture. These cells also exhibited increased expressions of cell-cycle inhibitory factors. Conclusions. The current results show trehalose inhibits malignant melanoma cell growth by inducing G2/M cell cycle arrest and apoptosis, suggesting trehalose as a potential candidate for a topical agent to inhibit proliferation of malignant tumor cells of the ocular surface. 1. Introduction Trehalose, (¦Á-glucopyranosyl-(1¡ú1)-¦Á-D-glucopyranoside), is a disaccharide isomer of sucrose that has a molecular weight of 342.29£¿Da with numerous interesting properties. This substance is widely present in animals, plants, insects, and microorganisms and plays an important role in preserving cells in situations that could lead to complete dehydration [1, 2]. Trehalose also reportedly has an inhibitory effect on the denaturation of protein and membranes in bacterial [3] and human cells [4], protects cryopreserved cells under freeze-dried conditions [5] and corneal epithelial cells under dry eye conditions [6], and may potentially have a therapeutic effect when treating the progression of Huntington¡¯s disease [7]. The safety and efficacy of topical instillation of trehalose eyedrops have been previously confirmed [8]. In addition to examining the protective effects of trehalose on epithelial cells, we have also previously reported that trehalose exhibited an inhibitory effect on the proliferation of fibroblasts and vascular endothelial cells [9, 10]. Even though trehalose has been shown to have various influences on cell
%U http://www.hindawi.com/journals/isrn.ophthalmology/2012/968493/