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10 results on '"Ruan, Zhi-Xiong"'

1. Correction to “BBA, a Derivative of 23-Hydroxybetulinic Acid, Potently Reverses ABCB1-Mediated Drug Resistance in Vitro and in Vivo”

Author

Zhang, Dong-Mei, primary, Shu, Chang, additional, Chen, Jun-Jiang, additional, Sodani, Kamlesh, additional, Wang, Jiao, additional, Bhatnagar, Jaya, additional, Lan, Ping, additional, Ruan, Zhi-Xiong, additional, Xiao, Zhi-Jie, additional, Ambudkar, Suresh V., additional, Chen, Wei-Min, additional, Chen, Zhe-Sheng, additional, and Ye, Wen-Cai, additional

Published
2023
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6. Bipiperidinyl derivatives of 23-hydroxybetulinic acid reverse resistance of HepG2/ADM and MCF-7/ADR cells

Author

Zhang, Dong-Mei, primary, Li, Ying-Jie, additional, Shu, Chang, additional, Ruan, Zhi-Xiong, additional, Chen, Wei-Min, additional, Yiu, Anita, additional, Peng, Ying-Hui, additional, Wang, Jiao, additional, Lan, Ping, additional, Yao, Zhe, additional, Fung, Kwok-Pui, additional, Fu, Li-Wu, additional, Chen, Zhe-Sheng, additional, and Ye, Wen-Cai, additional

Published
2013
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9. BBA, a Derivative of 23-Hydroxybetulinic Acid, Potently Reverses ABCB1-Mediated Drug Resistance in Vitro and in Vivo

Author

Zhang, Dong-Mei, primary, Shu, Chang, additional, Chen, Jun-Jiang, additional, Sodani, Kamlesh, additional, Wang, Jiao, additional, Bhatnagar, Jaya, additional, Lan, Ping, additional, Ruan, Zhi-Xiong, additional, Xiao, Zhi-Jie, additional, Ambudkar, Suresh V., additional, Chen, Wei-Min, additional, Chen, Zhe-Sheng, additional, and Ye, Wen-Cai, additional

Published
2012
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10. BBA, a Derivative of 23-Hydroxybetulinic Acid, Potently Reverses ABCB1-Mediated Drug Resistance in Vitroand in Vivo

Author

Zhang, Dong-Mei, Shu, Chang, Chen, Jun-Jiang, Sodani, Kamlesh, Wang, Jiao, Bhatnagar, Jaya, Lan, Ping, Ruan, Zhi-Xiong, Xiao, Zhi-Jie, Ambudkar, Suresh V., Chen, Wei-Min, Chen, Zhe-Sheng, and Ye, Wen-Cai

Abstract

23-O-(1,4′-Bipiperidine-1-carbonyl)betulinic acid (BBA), a synthetic derivative of 23-hydroxybetulinic acid (23-HBA), shows a reversal effect on multidrug resistance (MDR) in our preliminary screening. Overexpression of ATP-binding cassette (ABC) transporters such as ABCB1, ABCG2, and ABCC1 has been reported in recent studies to be a major factor contributing to MDR. Our study results showed that BBA enhanced the cytotoxicity of ABCB1 substrates and increased the accumulation of doxorubicin or rhodamine123 in ABCB1 overexpressing cells, but had no effect on non ABCB1 substrate, such as cisplatin; what’s more, BBA slightly reversed ABCG2-mediated resistance to SN-38, but did not affect the ABCC1-mediated MDR. Further studies on the mechanism indicated that BBA did not alter the expression of ABCB1 at mRNA or protein levels, but affected the ABCB1 ATPase activity by stimulating the basal activity at lower concentrations and inhibiting the activity at higher concentrations. In addition, BBA inhibited the verapamil-stimulated ABCB1 ATPase activity and the photolabeling of ABCB1 with [125I] iodoarylazidoprazosin in a concentration-dependent manner, indicating that BBA directly interacts with ABCB1. The docking study confirmed this notion that BBA could bind to the drug binding site(s) on ABCB1, but its binding position was only partially overlapping with that of verapamil or iodoarylazidoprazosin. Importantly, BBA increased the inhibitory effect of paclitaxel in ABCB1 overexpressing KB-C2 cell xenografts in nude mice. Taken together, our findings suggest that BBA can reverse ABCB1-mediated MDR by inhibiting its efflux function of ABCB1, which supports the development of BBA as a novel potential MDR reversal agent used in the clinic.

Published
2012
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