Purine analogue ENERGI-F706 induces apoptosis of 786-O renal carcinoma cells via 5′-adenosine monophosphate-activated protein kinase activation
| العنوان: | Purine analogue ENERGI-F706 induces apoptosis of 786-O renal carcinoma cells via 5′-adenosine monophosphate-activated protein kinase activation |
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| المؤلفون: | Chao‑Yu Hsu, Chun‑Hsiang Lin, Jiun Tsai Lin, Yi Fang Cheng, Han Min Chen, Shao-Hsuan Kao |
| المصدر: | Molecular Medicine Reports. 12:4566-4571 |
| بيانات النشر: | Spandidos Publications, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Adenosine monophosphate, Cancer Research, Cell cycle checkpoint, Bambusa, Apoptosis, AMP-Activated Protein Kinases, Biology, Kidney, Biochemistry, Cell Line, chemistry.chemical_compound, Cell Line, Tumor, Genetics, medicine, Humans, Viability assay, Protein kinase A, Molecular Biology, bcl-2-Associated X Protein, Caspase 3, Plant Extracts, AMPK, Epithelial Cells, Cell cycle, Antineoplastic Agents, Phytogenic, Adenosine, Caspase 9, Cell biology, Enzyme Activation, Gene Expression Regulation, Neoplastic, Pyrimidines, Proto-Oncogene Proteins c-bcl-2, Oncology, chemistry, Organ Specificity, Purines, S Phase Cell Cycle Checkpoints, Pyrazoles, Molecular Medicine, Poly(ADP-ribose) Polymerases, Tumor Suppressor Protein p53, Signal Transduction, medicine.drug |
| الوصف: | Purine compounds are known to activate 5'-adenosine monophosphate-activated protein kinase (AMPK), which has important roles in treatments for renal cell carcinoma. The present study was aimed to investigate the effects of the purine analogue ENERGI‑F706 on the human renal carcinoma cell line 786‑O and the underlying mechanisms. The results revealed that ENERGI‑F706 (0.2‑0.6 mg/ml) significantly decreased the cell viability to up to 36.4±2.4% of that of the control. Compared to 786‑O cells, ENERGI‑F706 exerted less suppressive effects on the viability of the human non‑tumorigenic renal cell line HK‑2. Flow cytometric analysis showed that ENERGI‑F706 contributed to cell cycle arrest at S‑phase and triggered apoptosis of 786‑O cells. Immunoblot analysis revealed that anti‑apoptotic B‑cell lymphoma 2 (Bcl‑2) levels were reduced and pro‑apoptotic Bcl‑2‑associated X protein levels were diminished. In addition, activation of caspase‑9, caspase‑3 and poly(adenosine diphosphate ribose) polymerase (PARP) was promoted in 786‑O cells in response to ENERGI‑F706. Effects of ENERGI‑F706 on AMPK cascades were investigated and the results showed that ENERGI‑F706 enhanced phosphorylation of AMPKα (T172) and p53 (S15), a downstream target of AMPK. In addition, the AMPK activation, p53 (S15) phosphorylation, reduction of Bcl‑2, cleavage of caspase‑3 and PARP as well as suppressed cell viability induced by ENERGI‑F706 were reversed in the presence of AMPK inhibitor compound C (dorsomorphin). In conclusion, the findings of the present study revealed that ENERGI‑F706 significantly suppressed the viability of 786‑O cells via induction of cell cycle arrest and apoptosis, attributing to AMPK and p53 activation and subsequent cell cycle regulatory and apoptotic signaling. It was therefore indicated that ENERGI‑F706 may be suitable for the treatment of renal cell carcinoma. |
| تدمد: | 1791-3004 1791-2997 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6916914014a9c51fca96c9b61c0669bcTest https://doi.org/10.3892/mmr.2015.3906Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6916914014a9c51fca96c9b61c0669bc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17913004 17912997 |
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