Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity

Liu, Xiaoyun; Zhang, Feiran; Shang, Jie; Liu, Yingying; Lv, Xiao‐Fei; Yuan, Jiani; Zhang, Tingting; Li, Kai; Lin, Xiaochun; Liu, Xiu; Lei, Qingqing; Fu, Xiaodong; Zhou, Jia‐Guo; Liang, Shi-Dong

doi:10.1038/s41419-018-0677-8

Cited by 38 publications

(29 citation statements)

References 31 publications

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“…5-FU reduces expression of anti-apoptotic protein Bcl-2. 47 An alternative mitochondrial mechanism leading to potentiate cell apoptosis through expression of p53 (a tumor suppressor gene) that binds to Bcl-2 and Bcl-XL proteins, therefore, activating Bak and Bax apoptotic proteins is advocated. 48 Therefore, in the present study induction of PC3 cell apoptosis may be, at least partly, due to elevation of p53 gene expression plus reduction of Bcl-2 protein.…”

Section: Resultsmentioning

confidence: 99%

Synergetic Impact of Combined 5-Fluorouracil and Rutin on Apoptosis in PC3 Cancer Cells through the Modulation of P53 Gene Expression

et al. 2019

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Purpose: Prostate cancer is as far the most prevalent male cancer. Rutin (a glycoside from quercetin flavonoid) displays antioxidant activity leading to cell apoptosis. Combined effects of rutin with the widely used anti-cancer drug, 5-fluorouracil (5-FU), on prostate cancer cell line (PC3) was investigated herein. Methods: Different concentrations of combined 5-FU and rutin were applied to PC3 cells compared to separate treatment for 48 hours. Cell viability, as well p53 gene expression respectively were assessed by MTT assay and real-time quantitative polymerase chain reaction (qPCR). Changes of Bcl-2 signal protein and apoptosis were determined using western blot and flow cytometry procedures, respectively. Clonogenic assay was used to colony counts assessment. Results: 50% inhibitory concentration (IC50) of separate cell treatment with either rutin and 5-FU respectively were 900 μM and 3Mm, while combination index (CI) of combined 5-FU /rutin application reached a level of synergistic effects (0.33). Combination of 5-FU/rutin enhanced apoptosis and p53 gene expression in PC3 cells. PC3 cell colony counts and Bcl-2 signaling protein were decreased by 5-FU/rutin combination. Conclusion: Synergistic effects of 5-FU/rutin combination on PC3 cells line enhanced apoptosis, p53 gene expression, and down-regulation of Bcl-2 protein, compared to control separate application. 5-FU/rutin combination does seem an interesting therapeutic pathway to be further investigated.

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Section: Resultsmentioning

confidence: 99%

Synergetic Impact of Combined 5-Fluorouracil and Rutin on Apoptosis in PC3 Cancer Cells through the Modulation of P53 Gene Expression

et al. 2019

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“…Inhibitor of apoptosis proteins (IAPs) family plays a critical role in regulating cell survival and death, which is closely associated with apoptosis resistance in a variety of cancer cells 28,29 . BIRC6 is the largest member of IAP family with a unique ubiquitin-conjugating domain 23,30 . The role of BIRC6 in AML has been well documented.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide

Wang

Fang

et al. 2019

oncol res

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Although arsenic trioxide (ATO) is a well-known antileukemic drug used for acute promyelocytic leukemia treatment, the development of ATO resistance is still a big challenge. We previously reported that microRNA-204 (miR-204) was involved in the regulation of acute myeloid leukemia (AML) cell apoptosis, but its role in chemoresistance is poorly understood. In the present study, we showed that miR-204 was significantly increased in AML cells after ATO treatment. Interestingly, the increased miR-204 level that was negatively correlated with ATO induced the decrease in cell viability and baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression. Overexpression of miR-204 potentiated ATO-induced AML cell growth inhibition and apoptosis. Furthermore, miR-204 directly targets to the 3′-UTR of BIRC6. Upregulation of miR-204 decreased BIRC6 luciferase activity and expression, which subsequently enhanced the expression of p53. Restoration of BIRC6 markedly reversed the effect of miR-204 on the regulation of AML cell sensitivity to ATO. Taken together, our study demonstrates that miR-204 decreases ATO chemoresistance in AML cells at least partially via promoting BIRC6/p53-mediated apoptosis. miR-204 represents a novel target of ATO, and upregulation of miR-204 may be a useful strategy to improve the efficacy of ATO in AML treatment.

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“…When a patient with cancer undergoes chemotherapy, proapoptotic Bax may be upregulated in response to sensing DNA damage. Bax in turn stimulates mitochondria to release cytochrome c. Cytochrome c is the major inducer of mitochondria (30). The ratio of Bax to Bcl-2 has been used in numerous studies in order to evaluate the level of apoptosis (43,44).…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis, known as programmed cell death, is closely associated with numerous anticancer reagents. When patients with cancer undergo chemotherapy, proapoptotic Bax may be upregulated in response to sensing DNA damage; and Bax in turn stimulates mitochondria to release cytochrome c. Cytochrome c is the major inducer of mitochondria apoptosis pathway (30). The protein expression of Bax and Bcl-2 were detected by western blotting.…”

Section: Ra and Irradiation Activate The Bax/mitochondria Cell Apoptomentioning

confidence: 99%

Rotundic acid enhances the impact of radiological toxicity on MCF-7 cells through the ATM/p53 pathway

Wang

Sun

et al. 2018

Int J Oncol

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Although radiation therapy is a powerful anticancer modality, radiation- induced stress response and gene expression with adaptive resistance may severely compromise the effectiveness of radiation. The function of rotundic acid (RA) on inducing apoptosis in the human breast cancer cell line MCF-7 has been investigated in a previous study. In the present study, the combined effect of chemotherapy and radiotherapy on reducing side effects was examined. The results of an MTT assay revealed that radiation (0.5, 2 and 10 Gy) effectively inhibit MCF-7 cell viability in a dose-dependent manner, consistent with the effects of RA (2, 5 and 12.5 µM). Interestingly, a lower dose of radiation (1 Gy) combined with RA (5 µM) exhibited a greater inhibition efficiency compared with a high dose of radiation alone. Flow cytometry revealed that radiation combined with RA induced the apoptosis of MCF-7 cells. Using western blotting, it was demonstrated that radiation induced the expression of ataxia-telangiectasia mutated (ATM) and p53 protein, and that RA enhanced this effect. On examining the potential underlying mechanism, it was revealed that radiation and RA combined induce Bcl-2-associated X protein expression and cell apoptosis in MCF-7 cells. An ATM inhibitor was able to restore the effect of radiation and RA on inducing MCF-7 cell apoptosis. These results suggest that the ATM/p53 pathway directly participates in radiation and RA-induced apoptosis in MCF-7 cells. RA has the potential for development as a novel drug for the treatment of human breast cancer combined with radiation therapy, given that the combined side effects are reduced.

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Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity

Cited by 38 publications

References 31 publications

Synergetic Impact of Combined 5-Fluorouracil and Rutin on Apoptosis in PC3 Cancer Cells through the Modulation of P53 Gene Expression

Synergetic Impact of Combined 5-Fluorouracil and Rutin on Apoptosis in PC3 Cancer Cells through the Modulation of P53 Gene Expression

MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide

Rotundic acid enhances the impact of radiological toxicity on MCF-7 cells through the ATM/p53 pathway

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