التفاصيل البيبلوغرافية
| العنوان: |
Purine analogue ENERGI-F706 induces apoptosis of 786-O renal carcinoma cells via 5'-adenosine monophosphate-activated protein kinase activation. |
| المؤلفون: |
CHAO-YU HSU, CHUN-HSIANG LIN, JIUN-TSAI LIN, YI-FANG CHENG, HAN-MIN CHEN, SHAO-HSUAN KAO |
| المصدر: |
Molecular Medicine Reports; 2015, Vol. 12 Issue 3, p4566-4571, 6p |
| مصطلحات موضوعية: |
RENAL cancer, APOPTOSIS, CANCER cells, ADENOSINE monophosphate, PROTEIN kinases |
| مستخلص: |
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 AMPKa (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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
