Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:A novel podophyllotoxin derivative (YB-1EPN) induces apoptosis and down-regulates express of P-glycoprotein in multidrug resistance cell line KBV200. 1987 73

Multidrug resistance (MDR) is a major obstacle to the chemotherapeutic treatment of breast cancer. Germacrone, the main component of Rhizoma Curcuma, has been shown to possess antitumor, anti-inflammatory and immunomodulatory properties. The aim of the present study was to investigate the effect of germacrone on MCF-7/Adriamycin (ADR) multidrug-resistant human breast cancer cells. The treatment of MCF-7/ADR cells with a combination of germacrone and ADR resulted in an increase in cytotoxicity compared with that of ADR alone, as determined using an MTT assay. Flow cytometric analysis revealed that germacrone promoted cell apoptosis in a dose-dependent manner, whilst treatment with germacrone plus ADR enhanced the apoptotic effect synergistically. Furthermore, the results from the western blot analysis demonstrated that augmenting ADR treatment with germacrone resulted in a reduction of anti-apoptotic protein expression levels (bcl-2) and enhancement of pro-apoptotic protein expression levels (p53 and bax) in MCF-7/ADR cells compared with the levels achieved by treatment with ADR alone. In addition, germacrone significantly reduced the expression of P-glycoprotein via the inhibition of the multidrug resistance 1 (MDR1) gene promoter. These findings demonstrate that germacrone has a critical role against MDR and may be a novel MDR reversal agent for breast cancer chemotherapy.
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PMID:Germacrone reverses Adriamycin resistance through cell apoptosis in multidrug-resistant breast cancer cells. 2528 68


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