Coniferyl aldehyde reduces radiation damage through increased protein stability of heat shock transcriptional factor 1 by phosphorylation.
OBJECTIVE
We previously screened natural compounds and found that coniferyl aldehyde (CA) was identified as an inducer of HSF1. In this study, we further examined the protective effects of CA against ionizing radiation (IR) in normal cell system.


METHODS
Western blotting and reverse transcription-polymerase chain reaction tests were performed to evaluate expression of HSF1, HSP27, and HSP70 in response to CA. Cell death and cleavage of PARP and caspase-3 were analyzed to determine the protective effects of CA in the presence of IR or taxol. The protective effects of CA were also evaluated using animal models.


RESULTS
CA increased stability of the HSF1 protein by phosphorylation at Ser326, which was accompanied by increased expression of HSP27 and HSP70. HSF1 phosphorylation at Ser326 by CA was mediated by EKR1/2 activation. Cotreatment of CA with IR or taxol in normal cells induced protective effects with phosphorylation- dependent patterns at Ser326 of HSF1. The decrease in bone marrow (BM) cellularity and increase of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive BM cells by IR were also significantly inhibited by CA in mice (30.6% and 56.0%, respectively). A549 lung orthotopic lung tumor model indicated that CA did not affect the IR-mediated reduction of lung tumor nodules, whereas CA protected normal lung tissues from the therapeutic irradiation.


CONCLUSIONS
These results suggest that CA may be useful for inducing HSF1 to protect against normal cell damage after IR or chemotherapeutic agents.
Graduate School of Pharmaceutical Sciences, Ewha Women's University, Seoul, Korea.
Seo-Young
SY
Kim
Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Hae-June
HJ
Lee
Graduate School of Pharmaceutical Sciences, Ewha Women's University, Seoul, Korea.
Joo-Won
JW
Nam
Graduate School of Pharmaceutical Sciences, Ewha Women's University, Seoul, Korea.
Eun-Kyoung
EK
Seo
Graduate School of Pharmaceutical Sciences, Ewha Women's University, Seoul, Korea. Electronic address: yslee0425@ewha.ac.kr.
Yun-Sil
YS
Lee
D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D008175:Lung Neoplasms / Q000532:radiotherapy; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014916:Whole-Body Irradiation / Q000379:methods
D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D012333:RNA, Messenger; D011837:Radiation-Protective Agents; D014157:Transcription Factors; C075384:coniferaldehyde; D000171:Acrolein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D017239:Paclitaxel