| Autor: |
Mendonca MS; Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. mmendonc@iupui.edu, Chin-Sinex H, Gomez-Millan J, Datzman N, Hardacre M, Comerford K, Nakshatri H, Nye M, Benjamin L, Mehta S, Patino F, Sweeney C |
| Jazyk: |
angličtina |
| Zdroj: |
Radiation research [Radiat Res] 2007 Dec; Vol. 168 (6), pp. 689-97. |
| DOI: |
10.1667/RR1128.1 |
| Abstrakt: |
Human cancers have multiple alterations in cell signaling pathways that promote resistance to cytotoxic therapy such as X rays. Parthenolide is a sesquiterpene lactone that has been shown to inhibit several pro-survival cell signaling pathways, induce apoptosis, and enhance chemotherapy-induced cell killing. We investigated whether parthenolide would enhance X-ray-induced cell killing in radiation resistant, NF-kappaB-activated CGL1 cells. Treatment with 5 microM parthenolide for 48 to 72 h inhibited constitutive NF-kappaB binding and cell growth, reduced plating efficiency, and induced apoptosis through stabilization of p53 (TP53), induction of the pro-apoptosis protein BAX, and phosphorylation of BID. Parthenolide also enhanced radiation-induced cell killing, increasing the X-ray sensitivity of CGL1 cells by a dose modification factor of 1.6. Flow cytometry revealed that parthenolide reduced the percentage of X-ray-resistant S-phase cells due to induction of p21 waf1/cip1 (CDKN1A) and the onset of G1/S and G2/M blocks, but depletion of radioresistant S-phase cells does not explain the observed X-ray sensitization. Further studies demonstrated that the enhancement of X-ray-induced cell killing by parthenolide is due to inhibition of split-dose repair. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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