Panduratin A Inhibits Cell Proliferation by Inducing G0/G1 Phase Cell Cycle Arrest and Induces Apoptosis in Breast Cancer Cells

Liu, Qiuming,Cao, Yali,Zhou, Ping,Gui, Shimin,Wu, Xiaobo,Xia, Yong,Tu, Jianhong The Korean Society of Applied Pharmacology 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.3

Because of the unsatisfactory treatment options for breast cancer (BC), there is a need to develop novel therapeutic approaches for this malignancy. One such strategy is chemotherapy using non-toxic dietary substances and botanical products. Studies have shown that Panduratin A (PA) possesses many health benefits, including anti-inflammatory, anti-bacterial, anti-oxidant and anticancer activities. In the present study, we provide evidence that PA treatment of MCF-7 BC cells resulted in a time- and dose-dependent inhibition of cell growth with an $IC_{50}$ of $15{\mu}M$ and no to little effect on normal human MCF-10A breast cells. To define the mechanism of these anti-proliferative effects of PA, we determined its effect critical molecular events known to regulate the cell cycle and apoptotic machinery. Immunofluorescence and flow cytometric analysis of Annexin V-FITC staining provided evidence for the induction of apoptosis. PA treatment of BC cells resulted in increased activity/expression of mitochondrial cytochrome C, caspases 7, 8 and 9 with a significant increase in the Bax:Bcl-2 ratio, suggesting the involvement of a mitochondrial-dependent apoptotic pathway. Furthermore, cell cycle analysis using flow cytometry showed that PA treatment of cells resulted in G0/G1 arrest in a dose-dependent manner. Immunoblot analysis data revealed that, in MCF-7 cell lines, PA treatment resulted in the dose-dependent (i) induction of $p21^{WAF1/Cip1}$ and p27Kip1, (ii) downregulation of Cyclin dependent kinase (CDK) 4 and (iii) decrease in cyclin D1. These findings suggest that PA may be an effective therapeutic agent against BC.

Panduratin A Inhibits Cell Proliferation by Inducing G0/G1 Phase Cell Cycle Arrest and Induces Apoptosis in Breast Cancer Cells

( Qiuming Liu,Yali Cao ),( Ping Zhou ),( Shimin Gui ),( Xiaobo Wu ),( Yong Xia ),( Jianhong Tu ) 한국응용약물학회 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.3

Because of the unsatisfactory treatment options for breast cancer (BC), there is a need to develop novel therapeutic approaches for this malignancy. One such strategy is chemotherapy using non-toxic dietary substances and botanical products. Studies have shown that Panduratin A (PA) possesses many health benefits, including anti-inflammatory, anti-bacterial, anti-oxidant and anticancer activities. In the present study, we provide evidence that PA treatment of MCF-7 BC cells resulted in a time- and dosedependent inhibition of cell growth with an IC< SUB >50< /SUB > of 15 μM and no to little effect on normal human MCF-10A breast cells. To define the mechanism of these anti-proliferative effects of PA, we determined its effect critical molecular events known to regulate the cell cycle and apoptotic machinery. Immunofluorescence and flow cytometric analysis of Annexin V-FITC staining provided evidence for the induction of apoptosis. PA treatment of BC cells resulted in increased activity/expression of mitochondrial cytochrome C, caspases 7, 8 and 9 with a significant increase in the Bax:Bcl-2 ratio, suggesting the involvement of a mitochondrial-dependent apoptotic pathway. Furthermore, cell cycle analysis using flow cytometry showed that PA treatment of cells resulted in G0/G1 arrest in a dose-dependent manner. Immunoblot analysis data revealed that, in MCF-7 cell lines, PA treatment resulted in the dosedependent (i) induction of p21^WAF1/Cip1 and p27Kip1, (ii) downregulation of Cyclin dependent kinase (CDK) 4 and (iii) decrease in cyclin D1. These findings suggest that PA may be an effective therapeutic agent against BC.

Convective Heat Transfer Coeicient Model Under Nanoluid Minimum Quantity Lubrication Coupled with Cryogenic Air Grinding Ti–6Al–4V

Jianchao Zhang,Wentao Wu,Changhe Li,Min Yang,Yanbin Zhang,Dongzhou Jia,Yali Hou,Runze Li,Huajun Cao,Hafiz Muhammad Ali 한국정밀공학회 2021 International Journal of Precision Engineering and Vol.8 No.4

Under the threat of serious environmental pollution and resource waste, sustainable development and green manufacturing have gradually become a new development trend. A new environmentally sustainable approach, namely, cryogenic air nanofluid minimum quantity lubrication (CNMQL), is proposed considering the unfavorable lubricating characteristic of cryogenic air (CA) and the deficient cooling performance of minimum quantity lubrication (MQL). However, the heat transfer mechanism of vortex tube cold air fraction by CNMQL remains unclear. The cold air fraction of vortex tubes influences the boiling heat transfer state and cooling heat transfer performance of nanofluids during the grinding process. Thus, a convective heat transfer coefficient model was established based on the theory of boiling heat transfer and conduction, and the numerical simulation of finite difference and temperature field in the grinding zone under different vortex tube cold air fractions was conducted. Simulation results demonstrated that the highest temperature initially declines and then rises with increasing cold air fraction. Afterward, this temperature reaches the lowest peak (192.7 °C) when the cold air fraction is 0.35. Experimental verification was conducted with Ti–6Al–4V to verify the convective heat transfer coefficient model. The results concluded that the low specific grinding energy (66.03 J/mm 3 ), high viscosity (267.8 cP), and large contact angle (54.01°) of nanofluids were obtained when the cold air fraction was 0.35. Meanwhile, the lowest temperature of the grinding zone was obtained (183.9 °C). Furthermore, the experimental results were consistent with the theoretical analysis, thereby verifying the reliability of the simulation model.

Whole transcriptome mapping reveals the lncRNA regulatory network of TFP5 treatment in diabetic nephropathy

Luo Hongyan,Yang Lirong,Zhang Guoqing,Bao Xi,Ma Danna,Li Bo,Cao Li,Cao Shilu,Liu Shunyao,Bao Li,E Jing,Zheng Yali 한국유전학회 2024 Genes & Genomics Vol.46 No.5

Background TFP5 is a Cdk5 inhibitor peptide, which could restore insulin production. However, the role of TFP5 in diabetic nephropathy (DN) is still unclear. Objective This study aims to characterize the transcriptome profiles of mRNA and lncRNA in TFP5-treated DN mice to mine key lncRNAs associated with TFP5 efficacy. Methods We evaluated the role of TFP5 in DN pathology and performed RNA sequencing in C57BL/6J control mice, C57BL/6J db/db model mice, and TFP5 treatment C57BL/6J db/db model mice. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were analyzed. WGCNA was used to screen hub-gene of TFP5 in treatment of DN. Results Our results showed that TFP5 therapy ameliorated renal tubular injury in DN mice. In addition, compared with the control group, the expression profile of lncRNAs in the model group was significantly disordered, while TFP5 alleviated the abnormal expression of lncRNAs. A total of 67 DElncRNAs shared among the three groups, 39 DElncRNAs showed a trend of increasing in the DN group and decreasing after TFP treatment, while the remaining 28 showed the opposite trend. DElncRNAs were enriched in glycosphingolipid biosynthesis signaling pathways, NF-κB signaling pathways, and complement activation signaling pathways. There were 1028 up-regulated and 1117 down-regulated DEmRNAs in the model group compared to control group, and 123 up-regulated and 153 down-regulated DEmRNAs in the TFP5 group compared to the model group. The DEmRNAs were involved in PPAR and MAPK signaling pathway. We confirmed that MSTRG.28304.1 is a key DElncRNA for TFP5 treatment of DN. TFP5 ameliorated DN maybe by inhibiting MSTRG.28304.1 through regulating the insulin resistance and PPAR signaling pathway. The qRT-PCR results confirmed the reliability of the sequencing data through verifying the expression of ENSMUST00000211209, MSTRG.31814.5, MSTRG.28304.1, and MSTRG.45642.14. Conclusion Overall, the present study provides novel insights into molecular mechanisms of TFP5 treatment in DN. Background TFP5 is a Cdk5 inhibitor peptide, which could restore insulin production. However, the role of TFP5 in diabetic nephropathy (DN) is still unclear. Objective This study aims to characterize the transcriptome profiles of mRNA and lncRNA in TFP5-treated DN mice to mine key lncRNAs associated with TFP5 efficacy. Methods We evaluated the role of TFP5 in DN pathology and performed RNA sequencing in C57BL/6J control mice, C57BL/6J db/db model mice, and TFP5 treatment C57BL/6J db/db model mice. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were analyzed. WGCNA was used to screen hub-gene of TFP5 in treatment of DN. Results Our results showed that TFP5 therapy ameliorated renal tubular injury in DN mice. In addition, compared with the control group, the expression profile of lncRNAs in the model group was significantly disordered, while TFP5 alleviated the abnormal expression of lncRNAs. A total of 67 DElncRNAs shared among the three groups, 39 DElncRNAs showed a trend of increasing in the DN group and decreasing after TFP treatment, while the remaining 28 showed the opposite trend. DElncRNAs were enriched in glycosphingolipid biosynthesis signaling pathways, NF-κB signaling pathways, and complement activation signaling pathways. There were 1028 up-regulated and 1117 down-regulated DEmRNAs in the model group compared to control group, and 123 up-regulated and 153 down-regulated DEmRNAs in the TFP5 group compared to the model group. The DEmRNAs were involved in PPAR and MAPK signaling pathway. We confirmed that MSTRG.28304.1 is a key DElncRNA for TFP5 treatment of DN. TFP5 ameliorated DN maybe by inhibiting MSTRG.28304.1 through regulating the insulin resistance and PPAR signaling pathway. The qRT-PCR results confirmed the reliability of the sequencing data through verifying the expression of ENSMUST00000211209, MSTRG.31814.5, MSTRG.28304.1, and MSTRG.45642.14. Conclusion Overall, the present study provides novel insights into molecular mechanisms of TFP5 treatment in DN.