Tryptanthrin inhibits MDR1 and reverses doxorubicin resistance in breast cancer cells

Journal Article · Fri Jun 22 00:00:00 EDT 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.04.107· OSTI ID:20991397

Yu, S -T ^[1]; Chen, T -M ^[2]; Tseng, S -Y ^[1]; Chen, Y -H ^[3]

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1. Graduate Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei 10051, Taiwan (China)
2. Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan (China)
3. Graduate Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei 10051, Taiwan (China) and National Center of Excellence for Clinical Trial and Research, College of Medicine, National Taiwan University, Taipei 10051, Taiwan (China)

Development of agents to overcome multidrug resistance (MDR) is important in cancer chemotherapy. Up to date, few chemicals have been reported to down-regulate MDR1 gene expression. We evaluated the effect of tryptanthrin on P-glycoprotein (P-gp)-mediated MDR in a breast cancer cell line MCF-7. Tryptanthrin could depress overexpression of MDR1 gene. We observed reduction of P-gp protein in parallel with decreases in mRNA in MCF-7/adr cells treated with tryptanthrin. Tryptanthrin suppressed the activity of MDR1 gene promoter. Tryptanthrin also enhanced interaction of the nuclear proteins with the negatively regulatory CAAT region of MDR1 gene promoter in MCF-7/adr. It might result in suppression of MDR1 gene. In addition, tryptanthrin decreased the amount of mutant p53 protein with decreasing mutant p53 protein stability. It might contribute to negative regulation of MDR1 gene. In conclusion, tryptanthrin exhibited MDR reversing effect by down-regulation of MDR1 gene and might be a new adjuvant agent for chemotherapy.

• OSTI ID: 20991397
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 358, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2007.04.107; PII: S0006-291X(07)00775-9; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

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