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

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.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6916914014a9c51fca96c9b61c0669bcTest
https://doi.org/10.3892/mmr.2015.3906Test

المؤلفون: Tian‑Zhi Zhao, Ding‑Guo Guan, Sheng‑Fang Liao, Han‑Min Chen

المصدر: Molecular medicine reports. 12(5)

مصطلحات موضوعية: Cancer Research, endocrine system diseases, Paclitaxel, Cell, Antineoplastic Agents, macromolecular substances, Pharmacology, Biology, Biochemistry, chemistry.chemical_compound, Glioma, Cell Line, Tumor, Genetics, medicine, Temozolomide, Humans, Molecular Biology, Brain Neoplasms, organic chemicals, Glucose transporter, Brain, Drug Synergism, Cell cycle, medicine.disease, Dacarbazine, medicine.anatomical_structure, Glucose, Oncology, chemistry, Apoptosis, Cell culture, Drug Resistance, Neoplasm, Molecular Medicine, medicine.drug

الوصف: Malignant gliomas, which comprise the most common type of primary malignant brain tumor, are associated with a poor prognosis and quality of life. Paclitaxel (Taxol) and temozolomide (TMZ) are Food and Drug Administration‑approved anticancer agents, which are known to have therapeutic applications in various malignancies. However, similar to other chemotherapeutic agents, the development of resistance to TMZ and Taxol is common. The aim of the present study was to investigate the regulation of glucose metabolism by TMZ and Taxol in glioma cells. The results demonstrated that glioma cells exhibit decreased glucose uptake and lactate production in response to treatment with TMZ; however, glucose metabolism was increased in response to Taxol treatment. Following analysis of TMZ‑ and Taxol‑resistant cell lines, it was reported that glucose metabolism was decreased in the TMZ‑resistant cells, but was increased in the Taxol‑resistant cells. Notably, a combination of TMZ and Taxol exerted synergistic inhibitory effects on Taxol‑resistant glioma cells. However, the synergistic phenotype was not observed following treatment with a combination of 5‑fluorouracil and Taxol. Furthermore, restoration of glucose metabolism by overexpression of glucose transporter 1 in Taxol‑resistant cells resulted in regained resistance to Taxol. Therefore, the present study proposes a novel mechanism accounting for the synergistic effects of Taxol and TMZ co‑treatment, which may contribute to the development of therapeutic strategies for overcoming chemoresistance in patients with cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc2c042fe30b61ca8da419c3d2858eb6Test
https://pubmed.ncbi.nlm.nih.gov/26459853Test

المؤلفون: DING-GUO GUAN¹ ggdingguo789@126.com, HAN-MIN CHEN¹, SHENG-FANG LIAO¹, TIAN-ZHI ZHAO²

المصدر: Molecular Medicine Reports. 2015, Vol. 12 Issue 5, p7705-7711. 7p.

مصطلحات موضوعية: *BRAIN cancer, *GLIOMAS, *QUALITY of life, *ANTINEOPLASTIC agents, *GLUCOSE metabolism

مستخلص: Malignant gliomas, which comprise the most common type of primary malignant brain tumor, are associated with a poor prognosis and quality of life. Paclitaxel (Taxol) and temozolomide (TMZ) are Food and Drug Administration-approved anticancer agents, which are known to have therapeutic applications in various malignancies. However, similar to other chemotherapeutic agents, the development of resistance to TMZ and Taxol is common. The aim of the present study was to investigate the regulation of glucose metabolism by TMZ and Taxol in glioma cells. The results demonstrated that glioma cells exhibit decreased glucose uptake and lactate production in response to treatment with TMZ; however, glucose metabolism was increased in response to Taxol treatment. Following analysis of TMZ- and Taxol-resistant cell lines, it was reported that glucose metabolism was decreased in the TMZ-resistant cells, but was increased in the Taxol-resistant cells. Notably, a combination of TMZ and Taxol exerted synergistic inhibitory effects on Taxol-resistant glioma cells. However, the synergistic phenotype was not observed following treatment with a combination of 5-fluorouracil and Taxol. Furthermore, restoration of glucose metabolism by overexpression of glucose transporter 1 in Taxol-resistant cells resulted in regained resistance to Taxol. Therefore, the present study proposes a novel mechanism accounting for the synergistic effects of Taxol and TMZ co-treatment, which may contribute to the development of therapeutic strategies for overcoming chemoresistance in patients with cancer. [ABSTRACT FROM AUTHOR]