کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10749972 | 1050296 | 2015 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Sub-chronic administration of LY294002 sensitizes cervical cancer cells to chemotherapy by enhancing mitochondrial JNK signaling
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Chemo-sensitization is used to improve the efficacy of chemotherapeutic agents against cancers, and understanding the precise molecular mechanisms of chemo-sensitization could lead to safer and more effective approaches to treat cancer. We have previously demonstrated that mitochondrial c-Jun N-terminal Kinase (JNK) signaling is a critical component of cell death. Mitochondrial JNK signaling is coordinated on the scaffold protein Sab. In this work, we developed a sub-chronic chemo-sensitization model by exposing HeLa cells to low-dose (2 μM) LY294002. We found that this treatment increased Sab expression on mitochondria, an effect not observed in acute exposures. To examine the role of Sab in chemo-sensitization, we ectopically expressed and silenced Sab in HeLa cells. We found that elevating Sab levels in HeLa cells increased the efficacy of chemotherapeutic agents, paclitaxel and cisplatin, while silencing Sab decreased the sensitivity of cells towards these agents. The effect of Sab-mediated signaling appeared to be dependent upon mitogen dependent protein kinases (MAPKs) as ablation of Sab's MAPK-binding motifs prevented chemo-sensitization. These results suggest that mitochondrial JNK signaling is an adaptable signaling pathway that can be enhanced or restored in cancer cells to improve therapeutic efficacy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 463, Issue 4, 7 August 2015, Pages 538-544
Journal: Biochemical and Biophysical Research Communications - Volume 463, Issue 4, 7 August 2015, Pages 538-544
نویسندگان
Tara P. Chambers, Gilda M. Portalatin, Iru Paudel, Charles J. Robbins, Jeremy W. Chambers,