The traditional Chinese medical compound Rocaglamide protects nonmalignant primary cells from DNA damage-induced toxicity by inhibition of p53 expression.

Autor:	Becker MS; Tumorimmunology Program (D030), German Cancer Research Center (DKFZ), INF-280, D-69120 Heidelberg, Germany., Schmezer P; Division of Epigenomics and Cancer Risk Factors, German Cancer Research Centre (DKFZ), INF-280, D-69120 Heidelberg, Germany., Breuer R; Tumorimmunology Program (D030), German Cancer Research Center (DKFZ), INF-280, D-69120 Heidelberg, Germany., Haas SF; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany., Essers MA; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany., Krammer PH; Tumorimmunology Program (D030), German Cancer Research Center (DKFZ), INF-280, D-69120 Heidelberg, Germany., Li-Weber M; Tumorimmunology Program (D030), German Cancer Research Center (DKFZ), INF-280, D-69120 Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	Cell death & disease [Cell Death Dis] 2014 Jan 16; Vol. 5, pp. e1000. Date of Electronic Publication: 2014 Jan 16.
DOI:	10.1038/cddis.2013.528
Abstrakt:	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.
Databáze:	MEDLINE
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