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44 results on '"Cai, Chao‐Yun"'

17. Cycloruthenated Self‐Assembly with Metabolic Inhibition to Efficiently Overcome Multidrug Resistance in Cancers

Author

Li, Jia, primary, Zeng, Leli, additional, Wang, Zheng, additional, Chen, Hengxing, additional, Fang, Shuo, additional, Wang, Jinquan, additional, Cai, Chao‐Yun, additional, Xing, Enming, additional, Liao, Xinxing, additional, Li, Zhi‐Wei, additional, Ashby, Charles R., additional, Chen, Zhe‐Sheng, additional, Chao, Hui, additional, and Pan, Yihang, additional

Published
2021
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18. VKNG-1 Antagonizes ABCG2-Mediated Multidrug Resistance via p-AKT and Bcl-2 Pathway in Colon Cancer: In Vitro and In Vivo Study

Author

Narayanan, Silpa, primary, Fan, Ying-Fang, additional, Gujarati, Nehaben A., additional, Teng, Qiu-Xu, additional, Wang, Jing-Quan, additional, Cai, Chao-Yun, additional, Yang, Yuqi, additional, Chintalapati, Anirudh J., additional, Lei, Yixiong, additional, Korlipara, Vijaya L., additional, and Chen, Zhe-Sheng, additional

Published
2021
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41. Selonsertib (GS-4997), an ASK1 inhibitor, antagonizes multidrug resistance in ABCB1- and ABCG2-overexpressing cancer cells.

Author

Ji, Ning, Yang, Yuqi, Cai, Chao-Yun, Lei, Zi-Ning, Wang, Jing-Quan, Gupta, Pranav, Shukla, Suneet, Ambudkar, Suresh V, Kong, Dexin, and Chen, Zhe-Sheng

Subjects
*PROTEIN metabolism, *ADENOSINE triphosphatase, *ANTINEOPLASTIC agents, *CELL lines, *COLON tumors, *COMPARATIVE studies, *DRUG resistance, *DRUG resistance in cancer cells, *EPITHELIAL cells, *LUNG cancer, *LUNG tumors, *MATHEMATICAL models, *RESEARCH methodology, *MEDICAL cooperation, *MONOCLONAL antibodies, *PACLITAXEL, *PROTEINS, *RESEARCH, *SQUAMOUS cell carcinoma, *TRANSFERASES, *TUMORS, *THEORY, *EVALUATION research, *PROTEIN kinase inhibitors, *MITOXANTRONE, *CHEMICAL inhibitors, *PHARMACODYNAMICS
Abstract

Overexpression of ATP-binding cassette (ABC) transporters is one of the most important mechanisms responsible for the development of multidrug resistance (MDR). Selonsertib, a serine/threonine kinase inhibitor, targets apoptosis signal-regulating kinase 1 (ASK1) and is now in phase III clinical trial for the treatment of non-alcoholic steatohepatitis (NASH). In this study, we investigated whether selonsertib could reverse MDR-mediated by ABC transporters, including ABCB1, ABCG2, ABCC1 and ABCC10. The results showed that selonsertib significantly reversed ABCB1- and ABCG2-mediated MDR, but not MDR-mediated by ABCC1 or ABCC10. Mechanism studies indicated that the reversal effect of selonsertib was related to the attenuation of the efflux activity of ABCB1 and ABCG2 transporters, without the protein level decrease or change in the subcellular localization of ABCB1 or ABCG2. Selonsertib stimulated the ATPase activity of ABCB1 and ABCG2 in a concentration-dependent manner, and in silico docking study showed selonsertib could interact with the substrate-binding sites of both ABCB1 and ABCG2. This study provides a clue into a novel treatment strategy, which includes a combination of selonsertib with antineoplastic drugs to attenuate MDR-mediated by ABCB1 or ABCG2 in cancer cells overexpressing these transporters. [ABSTRACT FROM AUTHOR]

Published
2018
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42. Mobocertinib antagonizes multidrug resistance in ABCB1- and ABCG2-overexpressing cancer cells: in vitro and in vivo studies.

Author

Dong XD, Zhang M, Teng QX, Lei ZN, Cai CY, Wang JQ, Wu ZX, Yang Y, Chen X, Guo H, and Chen ZS

Abstract

Overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1 and ABCG2, strongly correlates with multidrug resistance (MDR), rendering cancer chemotherapy ineffective. Exploration and identification of novel inhibitors targeting ABCB1 and ABCG2 are necessary to overcome the related MDR. Mobocertinib is an approved EGFR/HER2 inhibitor for non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. This study demonstrates that mobocertinib can potentially reverse ABCB1- and ABCG2-mediated MDR. Our findings indicate a strong interaction between mobocertinib and these two proteins, supported by its high binding affinity with ABCB1 and ABCG2 models. Through inhibiting the drug efflux function of ABCB1 and ABCG2, mobocertinib facilitates substrate drugs accumulation, thereby re-sensitizing substrate drugs in drug-resistant cancer cells. Additionally, mobocertinib inhibited the ATPase activity of ABCB1 and ABCG2 without changing the expression levels or subcellular localization. In the tumor-bearing mouse model, mobocertinib boosted the antitumor effect of paclitaxel and topotecan, resulting in tumor regression. In summary, our study uncovers a novel potential for repurposing mobocertinib as a dual inhibitor of ABCB1 and ABCG2, and suggests the combination of mobocertinib with substrate drugs as a strategy to counteract MDR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Zhe-Sheng Chen is an editorial board member of Cancer Letters., (Copyright © 2024. Published by Elsevier B.V.)

Published
2024
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43. Developing 3-(2-Isocyano-6-methylbenzyl)-1 H -indole Derivatives to Enhance the Susceptibility of Serratia marcescens by Occluding Quorum Sensing.

Author

Wang J, Yang JY, Durairaj P, Wang W, Tang S, Wang D, Cai CY, and Jia AQ

Subjects
Prodigiosin pharmacology, Prodigiosin metabolism, Molecular Docking Simulation, Anti-Bacterial Agents chemistry, Virulence Factors metabolism, Indoles pharmacology, Quorum Sensing, Serratia marcescens metabolism
Abstract

Quorum sensing (QS) inhibition is recognized as a novel antimicrobial target for infections caused by drug-resistant pathogens and is an attractive strategy for antipathogenic agent development. We designed and synthesized three parts of 3-(2-isocyanobenzyl)-1 H -indole derivatives and tested their activity as novel quorum sensing inhibitors (QSIs). 3-(2-Isocyanobenzyl)-1 H -indole derivatives demonstrated promising QS, biofilms, and prodigiosin inhibitory activities against Serratia marcescens at subminimum inhibitory concentrations (sub-MICs). In particular, 3-(2-isocyano-6-methylbenzyl)-1 H -indole (IMBI, 32 ) was identified as the best candidate based on several screening assays, including biofilm and prodigiosin inhibition. Further studies demonstrated that exposure to IMBI at 1.56 μg/mL to S. marcescens NJ01 significantly inhibited the formation of biofilms by 42%. The IMBI treatment on S. marcescens NJ01 notably enhanced the susceptibility of the formed biofilms, destroying the architecture of the biofilms by up to 40%, as evidenced by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). For interference of virulence factors in S. marcescens NJ01, IMBI at 3.12 μg/mL inhibited the activity of protease and extracellular polysaccharides (EPS) by 17% and 51%, respectively, which were higher than that of the positive control vanillic acid (VAN). Furthermore, IMBI downregulated the expression of QS- and biofilm-related genes fimA , bsmA , pigP , flhC , rssB , fimC , and rsmA by 1.02- to 2.74-fold. To confirm these findings, molecular docking was performed, which indicated that the binding of IMBI to SmaR, RhlI, RhlR, LasR, and CviR could antagonize the expression of QS-linked traits. In addition, molecular dynamic simulations (MD) and energy calculations indicated that the binding of receptors with IMBI was extremely stable. The biofilms of S. marcescens NJ01 were markedly reduced by 50% when IMBI (0.39 μg/mL) was combined with kanamycin (0.15 μg/mL). In conclusion, this study highlights the potency of IMBI in inhibiting the virulence factors of S. marcescens . IMBI has all the potential to be developed as an effective and efficient QS inhibitor and antibiofilm agent in order to restore or improve antimicrobial drug sensitivity.

Published
2023
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44. Y 6 , an Epigallocatechin Gallate Derivative, Reverses ABCG2-Mediated Mitoxantrone Resistance.

Author

Zhao RQ, Wen Y, Gupta P, Lei ZN, Cai CY, Liang G, Yang DH, Chen ZS, and Xie YA

Abstract

Multidrug resistance is reported to be related to the transmembrane transportation of chemotherapeutic drugs by adenosine triphosphate-binding cassette (ABC) transporters. ABC subfamily G member 2 (ABCG2) is a member of the ABC transporter superfamily proteins, which have been implicated as a key contributor to the development of multidrug resistance in cancers. A new epigallocatechin gallate derivative, Y 6 was synthesized in our group. Our previous study revealed that Y 6 increased the sensitivity of drug-resistant cells to doxorubicin, which was associated with down-regulation of P-glycoprotein expression. In this study, we further determine whether Y 6 could reverse ABCG2-mediated multidrug resistance. Results showed that, at non-toxic concentrations, Y 6 significantly sensitized drug-selected non-small cell lung cancer cell line NCI-H460/MX20 to substrate anticancer drugs mitoxantrone, SN-38, and topotecan, and also sensitized ABCG2-transfected cell line HEK293/ABCG2-482-R2 to mitoxantrone and SN-38. Further study demonstrated that Y 6 significantly increased the accumulation of [ 3 H]-mitoxantrone in NCI-H460/MX20 cells by inhibiting the transport activity of ABCG2, without altering the expression levels and the subcellular localization of ABCG2. Furthermore, Y 6 stimulated the adenosine triphosphatase activity with a concentration-dependent pattern under 20 μM in membranes overexpressing ABCG2. In addition, Y 6 exhibited a strong interaction with the human ABCG2 transporter protein. Our findings indicate that Y 6 may potentially be a novel reversal agent in ABCG2-positive drug-resistant cancers.

Published
2019
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