کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2579762 | 1561583 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Nephrotoxicity of epigenetic inhibitors used for the treatment of cancer
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کلمات کلیدی
CDKDnmtCDKN1ACFZHEK293HDACNRKNGSCbzTSAEpigenetic inhibitors3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide - 3- (4،5-dimethylthiazol-2-yl) -2،5-difenyltetrazolium bromide5-Aza - 5-نهDMSO - DMSODNA methyltransferase - DNA متیل ترانسفرازMTT - MTTchromatin immunoprecipitation - ایمن سازی کروماتینTrichostatin A - تریکوستاتین ANext-generation sequencing - تعیین توالی نسل بعدیDimethyl sulfoxide - دیمتیل سولفواکسیدProstate cancer - سرطان پروستاتKidney cells - سلول های کلیهcyclin-dependent kinase inhibitor 1A - مهار کننده 1A کیناز وابسته به کینازNephrotoxicity - نفخ سمیHistone acetyltransferase - هیستون استیل ترانسفرازhistone deacetylase - هیستون داستیلازCHiP - چیپCarfilzomib - کارفیلزیمیبHAT - کلاهhuman embryonic kidney 293 - کلیه جنینی انسان 293normal rat kidney - کلیه موش طبیعیcyclin-dependent kinase - کییناز وابسته به سیکلین
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
This study determined the anti-neoplastic activity and nephrotoxicity of epigenetic inhibitors in vitro. The therapeutic efficacy of epigenetic inhibitors was determined in human prostate cancer cells (PC-3 and LNCaP) using the DNA methyltransferase inhibitor 5-aza-2ʹ-deoxycytidine (5-Aza) and the histone deacetylase inhibitor trichostatin A (TSA). Cells were also treated with carbamazepine (CBZ), an anti-convulsant with histone deacetylase inhibitor-like properties. 5-Aza, TSA or CBZ alone did not decrease MTT staining in PC-3 or LNCaP cells after 48 h. In contrast, docetaxel, a frontline chemotherapeutic induced concentration-dependent decreases in MTT staining. Pretreatment with 5-Aza or TSA increased docetaxel-induced cytotoxicity in LNCaP cells, but not PC-3 cells. TSA pretreatment also increased cisplatin-induced toxicity in LNCaP cells. Carfilzomib (CFZ), a protease inhibitor approved for the treatment of multiple myeloma had minimal effect on LNCaP cell viability, but reduced MTT staining 50% in PC-3 cells compared to control, and pretreatment with 5-Aza further enhanced toxicity. Treatment of normal rat kidney (NRK) and human embryonic kidney 293 (HEK293) cells with the same concentrations of epigenetic inhibitors used in prostate cancer cells significantly decreased MTT staining in all cell lines after 48 h. Interestingly, we found that the toxicity of epigenetic inhibitors to kidney cells was dependent on both the compound and the stage of cell growth. The effect of 5-Aza and TSA on DNA methyltransferase and histone deacetylase activity, respectively, was confirmed by assessing the methylation and acetylation of the CDK inhibitor p21. Collectively, these data show that combinatorial treatment with epigenetic inhibitors alters the efficacy of chemotherapeutics in cancer cells in a compound- and cell-specific manner; however, this treatment also has the potential to induce nephrotoxic cell injury.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 258, 25 October 2016, Pages 21-29
Journal: Chemico-Biological Interactions - Volume 258, 25 October 2016, Pages 21-29
نویسندگان
N.E. Scholpa, R.T. Kolli, M. Moore, R.D. Arnold, T.C. Glenn, B.S. Cummings,