Publications (2)4.24 Total impact
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Article: A novel podophyllotoxin derivative (YB-1EPN) induces apoptosis and down-regulates express of P-glycoprotein in multidrug resistance cell line KBV200.
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ABSTRACT: Our group synthesized a new potent anti-tumor podophyllotoxin derivative, YB-1EPN. In our study, we found that it was more potent than etoposide (VP-16). Interestingly, we found that the KBV200 cell line and K562/A02 cell line were rendered resistant towards VP-16 but not towards YB-1EPN. In vitro, both the cytotoxicity of YB-1EPN and its ability to inhibit KBV200 and K562/A02 cells were determined by MTT assay and growth curve. The IC(50) value of YB-1EPN on KBV200 cell was (2.52+/-0.28)microM in contrast to VP-16 (10.1+/-0.220)microM. And YB-1EPN showed a dose-dependent and broad-spectrum antiproliferative activity. Inducing apoptosis by YB-1EPN in KBV200 was assessed by various morphological and biochemical characteristics, including cell shrinkage, chromatin condensation, membrane blebbing, formation of apoptotic bodies, and DNA ladder formation. Rates of apoptosis and cell cycle were also checked through flow cytometry. Reverse transcription-polymerase chain reaction(RT-PCR) was used to detect mdr-1,p53,bcl-2,and bax gene expression. Western-blot assay was used to assess P-glycoprotein (P-gp) expression. We found that YB-1EPN could down-regulate expression level of the mdr-1, bcl-2, and up-regulate expression level of p53, and bax mRNA, as compared to the control. These results suggest that YB-1EPN has the potentiality to overcome P-glycoprotein-mediated multidrug resistance in the KBV200 cell line.European journal of pharmacology 10/2009; 627(1-3):69-74. · 2.59 Impact Factor -
Article: L1EPO, a novel podophyllotoxin derivative overcomes P-glycoprotein-mediated multidrug resistance in K562/A02 cell line.
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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), GI(50)>10 micromol/l. Consequently, L1EPO has the potential to overcome P-glycoprotein-mediated MDR in the K562/A02 cell line.Biological & Pharmaceutical Bulletin 04/2009; 32(4):609-13. · 1.66 Impact Factor
