Leptomycin B Increases Radiosensitization by Trichostain A in HeLa Cells / 대한방사선종양학회지

ABSTRACT

PURPOSE: Histone deacetylase inhibitors (HDIs) are emerging as potentially useful components of anticancer therapy and their radiosensitizing effects have become evident. Specific HDIs are now available that preferentially inhibit specific HDAC classes; TSA inhibits Class I and II HDACs, and SK7041 inhibits Class I HDACs. MATERIALS AND METHODS: We tested the differential radiosensitization induced by two different classes of HDIs in HeLa cells. We next tested the hypothesis that p53 expression in cancer cells may influence the susceptibility to HDIs by using pharmacologic modification of the p53 status under an isogenic background. RESULTS: It is interesting that p53 expression in the HeLa cells clearly increased the degree of radiosensitization by TSA compared to that of the class I specific inhibitor SK7041. This suggests that p53 may, in part, be responsible for the mechanistic role for the greater radiosensitization induced by Class I & II inhibitors compared to that of the class I specific inhibitors. Thus, these studies are useful in distinguishing between events mediated solely by the Class I HDACs versus those events involving the other classes of HDACs as well. CONCLUSION: The anticancer efficacy of targeting Class I and II HDACs, in conjunction with radiation therapy, may be further enhanced by the restoration of p53 expression.