Epigenetic modification potentially sensitizes heavy-ion therapy for malignancy

Saito, Katsuyo*; Funayama, Tomoo; Kobayashi, Yasuhiko; Murakami, Takashi*

Malignant melanoma is one of the most common cutaneous malignancies. Epigenetic modifiers, such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors, have emerged recently as promising anticancer agents and has been expected as a sensitizer for other cancer therapeutics including radiotherapy. In addition, the biological effects of the high linear energy transfer (LET) heavy-ion radiation are more pronounced than the low-LET radiation. These accumulating evidences allowed us to investigate whether the use of HDACi could sensitize melanoma cells for the heavy-ion therapy. Treatment of B16F10 melanoma cells with HDACi in combination with heavy-ion radiation provided enhanced anti-tumor effects. These data suggest that combination of HDACi together with heavy-ion therapy may provide improved therapeutic responses in melanoma patients.