Antitumor histone deacetylase inhibitors suppress cutaneous radiation syndrome: Implications for increasing therapeutic gain in cancer radiotherapy.
Radiotherapy is an effective treatment for head and neck, skin, anogenital, and breast cancers. However, radiation-induced skin morbidity limits the therapeutic benefits. A low-toxicity approach to selectively reduce skin morbidity without compromising tumor killing by radiotherapy is needed. We found that the antitumor agents known as histone deacetylase (HDAC) inhibitors (phenylbutyrate, trichostatin A, and valproic acid) could suppress cutaneous radiation syndrome. The effects of HDAC inhibitors in promoting the healing of wounds caused by radiation and in decreasing later skin fibrosis and tumorigenesis were correlated with suppression of the aberrant expression of radiation-induced transforming growth factor beta and tumor necrosis factor alpha. Our findings implicate that the inhibition of HDAC may provide a novel strategy to increase the therapeutic gain in cancer radiotherapy by not only inhibiting tumor growth but also protecting normal tissues.
Chung
Yih Lin
YL
Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, and School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. ylchung@mail.kfcc.org.tw
Wang
Ae-June
AJ
Yao
Lin-Fen
LF
D000107:Acetylation; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005355:Fibrosis; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology; D010654:Phenylbutyrates / Q000494:pharmacology; D011832:Radiation Injuries / Q000188:drug therapy*; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012260:Ribonucleases / Q000378:metabolism; D012867:Skin / Q000473:pathology / Q000528:radiation effects; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology; D014945:Wound Healing
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D010654:Phenylbutyrates; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C012589:trichostatin A; D014635:Valproic Acid; D012260:Ribonucleases