Search for effective hyperthermia sensitizer targeting nuclear stress bodies formation

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  • WATANABE Kazunori
    Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University

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  • 核内ストレス顆粒形成を標的とした効果的なハイパーサーミア増感剤の探索
  • カク ナイ ストレス カリュウ ケイセイ オ ヒョウテキ ト シタ コウカテキ ナ ハイパーサーミア ゾウカンザイ ノ タンサク

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Abstract

<p>【Background】</p><p>Hyperthermia therapy is a cancer treatment based on cell growth inhibition and apoptosis induced by heat stress. One of the problems of hyperthermia therapy is the reduction of therapeutic effect due to the thermal resistance mechanism. As one of the thermal resistance mechanisms, nuclear stress bodies containing HSF1 and SAFB are formed. In this study, we searched for a novel compound that enhances cell growth suppression by heat through suppressing the formation of SAFB granules.</p><p>【Methods】</p><p>We analyzed whether each compound induced more suppression of cell proliferation of cervical cancer cells, HeLa cells by heat stress. In addition, we confirmed whether HSF1 and SAFB granule formation was suppressed in the presence of the thermal sensitizers by immunostaining.</p><p>【Results】</p><p>The compound A, which inhibits the activity of protein A, was enhanced the suppression of cell proliferation of HeLa cells by heat stress. Furthermore, the compound A suppressed the formation of SAFB granules.</p><p>As a result of compound screening for searching thermal sensitizer, 13 compounds enhanced the suppression of cell proliferation of HeLa cells by heat stress. Among them, four compounds showed high suppression of cell proliferation of HeLa cells by heat stress.</p><p>【Conclusion】</p><p>In this study, we identified compound A which was enhanced thermal sensitivity and suppressed the formation of SAFB granule. In addition, we identified four compounds which was enhanced highly thermal sensitivity.</p>

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