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| Item Type: | Article |
|---|---|
| Title: | The traditional Chinese medical compound Rocaglamide protects nonmalignant primary cells from DNA damage-induced toxicity by inhibition of p53 expression |
| Creators Name: | Becker, M.S., Schmezer, P., Breuer, R., Haas, S.F., Essers, M.A., Krammer, P.H. and Li-Weber, M. |
| Abstract: | One of the main obstacles of conventional anticancer therapy is the toxicity of chemotherapeutics to normal tissues. So far, clinical approaches that aim to specifically reduce chemotherapy-mediated toxicities are rare. Recently, a number of studies have demonstrated that herbal extracts derived from traditional Chinese medicine (TCM) may reduce chemotherapy-induced side effects. Thus, we screened a panel of published cancer-inhibiting TCM compounds for their chemoprotective potential and identified the phytochemical Rocaglamide (Roc-A) as a candidate. We show that Roc-A significantly reduces apoptotic cell death induced by DNA-damaging anticancer drugs in primary human and murine cells. Investigation of the molecular mechanism of Roc-A-mediated protection revealed that Roc-A specifically blocks DNA damage-induced upregulation of the transcription factor p53 by inhibiting its protein synthesis. The essential role of p53 in Roc-A-mediated protection was confirmed by siRNA knockdown of p53 and by comparison of the effects of Roc-A on chemoprotection of splenocytes isolated from wild-type and p53-deficient mice. Importantly, Roc-A did not protect p53-deficient or -mutated cancer cells. Our data suggest that Roc-A may be used as an adjuvant to reduce the side effects of chemotherapy in patients with p53-deficient or -mutated tumors. |
| Keywords: | Chemoprotection, p53, Apoptosis, Rocaglamide, Anticancer Drug, TCM, Animals, Mice |
| Source: | Cell Death & Disease |
| ISSN: | 2041-4889 |
| Publisher: | Nature Publishing Group |
| Volume: | 5 |
| Page Range: | e1000 |
| Date: | January 2014 |
| Official Publication: | https://doi.org/10.1038/cddis.2013.528 |
| PubMed: | View item in PubMed |
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