[Possibilities of epigenetic anti-tumor therapy in in-vitro models]

Research during the past decade has shown that epigenetic events have a key role in carcinogenesis and tumour progression. Histone deacetylase inhibitors (HDACi) comprise structurally diverse compounds that are a group of targeted epigenetic anticancer agents. Here we explored the in vitro efficacy of HDACi such as sodium butyrate (BuNa), valproic acid (VaNa) and several novel HDAC inhibitors for the treatment of cancer. Both BuNa and VaNa inhibited cancer cell proliferation in a time--and dose-dependent fashion. In the present study we demonstrated the significant effect of two novel HDACi, Adipo or BuNHOH, able to induce apoptosis of cancer cells, but not of normal line. Since HDAC inhibitors have been proposed as radio--or chemosensitizers in cancer therapy, we have studied the radiosensitizing effect of sodium butyrate on cancer cells. The combination of BuNa and radiation significantly inhibited tumor cell growth. Besides, combining Cisplatin or Gemzar with HDAC inhibitors results in synergistic antiproliferative activity that could be therapeutically exploited. These results suggest that HDACi acts as an antitumor agent and that combining HDAC inhibitors with radio or--chemotherapeutic strategy may provide a novel chemotherapeutic treatment of cancers insensitive to traditional antitumor agents.