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Arzneimittelforschung 2012; 62(05): 236-242
DOI: 10.1055/s-0031-1301344
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

The Multidrug Resistant Modulator HZ08 Reverses Multidrug Resistance via P-glycoprotein Inhibition and Apoptosis Sensitization in Human Epidermoid Carcinoma Cell Line KBv200

Y.-L. Zhu
1   Department of Physiology, China Pharmaceutical University, Nanjing, P. R. China
,
J. Cen
2   Key Laboratory of Nature Medicine and Immune Engineering, Henan University, Kaifeng, P. R. China
,
Y.-Y. Zhang
1   Department of Physiology, China Pharmaceutical University, Nanjing, P. R. China
,
Y.-D. Feng
1   Department of Physiology, China Pharmaceutical University, Nanjing, P. R. China
,
Y. Yang
1   Department of Physiology, China Pharmaceutical University, Nanjing, P. R. China
,
Y.-M. Li
1   Department of Physiology, China Pharmaceutical University, Nanjing, P. R. China
,
W.-L. Huang
3   Center of Drug Discovery, China Pharmaceutical University, Nanjing, P. R. China
› Author Affiliations
Further Information

Publication History

received 21 October 2011

accepted 09 January 2012

Publication Date:
16 February 2012 (online)

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The Multidrug Resistant Modulator HZ08 Reverses Multidrug Resistance via P-glycoprotein Inhibition and Apoptosis Sensitization in Human Epidermoid Carcinoma Cell Line KBv200Arzneimittelforschung 2012; 62(05): e1-e1
DOI: 10.1055/s-0032-1306332

Abstract

Previous studies have demonstrated that the multidrug resistance modulator HZ08 has a strong multidrug resistance reversal effect in vitro and in vivo by inhibiting P-glycoprotein and multidrug resistance-associated protein 1 in K562/A02 and MCF-7/ADM cells, respectively. However, there are many other mechanisms responsible for resistance. In this study, MTT assay was used to examine the cytotoxicity and multidrug resistance reversal of HZ08 in KBV200 cells. It was also used to detect Rh123 and adriamycin accumulation in the presence of HZ08 to assess the effect on P-glycoprotein. Caspase-3 activity was analyzed under the incubation of HZ08 per se and in combination with vincristine. Results showed that HZ08 could increase the activity of caspase-3 with P-glycoprotein inhibition. Further studies revealed that HZ08 increased vincristine-induced apoptosis, characterized as an intrinsic apoptosis pathway with enhanced G2/M phase arrest, since HZ08 had an effect on the intrinsic apoptotic regulator Bcl-2 and Bax. Therefore, the outstanding reversal effect of HZ08 occurs not only through suppressing the P-glycoprotein function but also through activating the intrinsic apoptosis pathway.

Key words

HZ08 - multidrug resistance - P-glycoprotein - apoptosis - KBv200
 

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