L1EPO, a Novel Podophyllotoxin Derivative Overcomes P-Glycoprotein-Mediated Multidrug Resistance in K562/A02 Cell Line

• Chen Hong

  Medical College of Chinese People's Armed Police Forces Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard

• Wang Jing

  Medical College of Chinese People's Armed Police Forces

• Zhang Jingze

  Medical College of Chinese People's Armed Police Forces

• Wang Yizheng

  Medical College of Chinese People's Armed Police Forces Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard

• Cao Bo

  Medical College of Chinese People's Armed Police Forces

• Bai Shufang

  Medical College of Chinese People's Armed Police Forces

• Yu Peng-Fei

  Key Lab of New Drugs Design and Discovery of Liaoning Province, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University

• Bi Wenchao

  Medical College of Chinese People's Armed Police Forces

• Xie Wenli

  Medical College of Chinese People's Armed Police Forces

Abstract

The ineffectiveness of anticancer drugs is frequently observed in cancer chemotherapy. The resistance of tumor cells to various cytotoxic drugs is defined as multidrug resistance (MDR). The purpose of our present study was to investigate the inhibitory effects of L1EPO synthesized by our group on P-glycoprotein (P-gp)-mediated MDR in K562/A02 and KBv200 cell lines, which expressed high levels of P-gp. Both the cytotoxicity of the compound and its ability to inhibit K562/A02 and KBv200 cells were determined by sulforhodamine B sodium salt (SRB) assay. Morphologic apoptosis was detected by Hoechst33342 staining assay. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect mdr-1 gene transcription, and Western blot assay was used to assess P-gp expression. Interestingly, we found that the K562/A02 cell line was rendered resistant toward Adriamycin but not towards L1EPO when compared with the parental cells. Furthermore, L1EPO could down-regulate the mdr-1 gene, and it reduced the expression of P-gp and displayed a perfect dose dependence. Moreover, it had less cytotoxicity in normal human cell lines (fibroblast, VEC), GI₅₀>10 μmol/l. Consequently, L1EPO has the potential to overcome P-glycoprotein-mediated MDR in the K562/A02 cell line.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 32 (4), 609-613, 2009

  The Pharmaceutical Society of Japan

Keywords

• L1EPO
• Podophyllotoxin
• derivative
• multidrug resistance
• P-glycoprotein

Details

• CRID: 1390001204624263680
• NII Article ID: 110007160694
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.32.609
• ISSN: 13475215
• ISSN: 09186158
• NDL BIB ID: 10194238
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10194238
• Web Site: http://www.jstage.jst.go.jp/article/bpb/32/4/32_4_609/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2009266104
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed