کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1908678 1046679 2012 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
P38 MAP kinase functions as a switch in MS-275-induced reactive oxygen species-dependent autophagy and apoptosis in Human colon Cancer cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
P38 MAP kinase functions as a switch in MS-275-induced reactive oxygen species-dependent autophagy and apoptosis in Human colon Cancer cells
چکیده انگلیسی

MS-275 is a synthetic benzamide derivative of the histone deacetylase inhibitor and is currently in phase I/II clinical trials. Many reports have shown that the anti-tumor activity of MS-275 in several types of cancer is mainly attributable to its capacity to induce the apoptotic death of tumor cells. It remains unclear if autophagy is involved in MS-275 treatment of cancer cells. Here, we first show that MS-275 induces human colon cancer cell HCT116 autophagy as well as apoptosis. Short-term treatment (24 h) induced HCT116 cells to undergo autophagy with dependence on intracellular reactive oxygen species production and ERK activation. The activated reactive oxygen species/ERK signal promoted Atg7 protein expression, which triggered MS-275-induced cancer cell autophagy. However, after prolonged treatment with MS-275 (over 48 h), autophagic cells turned apoptotic, which was also dependent on reactive oxygen species generation. Interestingly, we found that p38 MAP kinase played a vital role in the switch from autophagy to apoptosis in MS-275-induced human colon cancer cells. High expression of p38 induced cell autophagy, but low expression resulted in apoptosis. In addition, observations in vivo are strongly consistent with the in vitro results. Therefore, these findings extend our understanding of the action of MS-275 in inducing cancer cell death and suggest that it may be a promising clinical chemotherapeutic agent with multiple effects.

Figure optionsDownload high-quality image (203 K)Download as PowerPoint slideHighlights
► MS-275-induced autophagy is reactive oxygen species dependent.
► A short-term MS-275 treatment induces HCT116 cell autophagy.
► A long-term MS-275 treatment can induce cancer cell apoptosis.
► P38 MAPK acts as a switch in MS-275-induced autophagy–apoptosis transition.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 53, Issue 3, 1 August 2012, Pages 532–543
نویسندگان
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