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Inhibitory effects of trehalose on malignant melanoma cell growth: implications for a novel topical anticancer agent
Takashi Kudo1, Kimio Takeuchi1, Yu-Ichi Ebina1
1Department of Opthalmology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Abstract:
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 ≧ 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.
Insights
Trehalose significantly inhibits malignant melanoma cell growth and proliferation. This natural compound induces cell cycle arrest and apoptosis, showing potential as a topical treatment for ocular surface tumors.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Malignant melanoma is a significant cause of cancer-related mortality.
- Novel therapeutic strategies are needed to combat melanoma progression, particularly for ocular surface tumors.
Purpose of the Study:
- To evaluate the anti-proliferative effects of trehalose on malignant melanoma cells.
- To investigate the underlying mechanisms of trehalose-induced growth inhibition.
Main Methods:
- Human malignant melanoma cells were cultured with varying trehalose concentrations and assessed using MTT assays.
- In vivo studies involved topical trehalose administration to melanoma-inoculated rats, followed by histopathological analysis.
- Flow cytometry was employed to analyze cell cycle distribution, apoptosis rates, and cell-cycle-related factors.
Main Results:
- Trehalose demonstrated significant inhibition of melanoma cell proliferation at concentrations of 5% and above.
- In vivo, trehalose treatment led to a significant reduction in tumor size in inoculated eyes.
- Flow cytometry revealed increased G2/M phase arrest and apoptosis in trehalose-treated melanoma cells, along with elevated levels of cell-cycle inhibitory factors.
Conclusions:
- Trehalose effectively inhibits malignant melanoma cell growth through G2/M cell cycle arrest and apoptosis induction.
- These findings suggest trehalose as a promising candidate for topical therapeutic applications against ocular surface malignant tumors.
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