Skip to main content

Levistolide A overcomes P-glycoprotein-mediated drug resistance in human breast carcinoma cells

Buy Article:

$51.00 plus tax (Refund Policy)

Abstract:

Abstract

Aim: The aim of the present study was to investigate the reversing effect of levistolide A (LA) on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in human breast carcinoma Bcap37/MDR1 cells. Methods: After chemotherapeutic drugs (adriamycin or vincristine) used alone or in combination with LA, cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazo-lium bromide assay and cell cycle distribution by flow cytometry. RT-PCR was used to detect MDR1 gene transcription and the Western blot assay was used to assess P-gp expression and the cleavages of poly(ADP-ribose) polymerase and caspase-3. Apoptosis was detected by terminal transferase-mediated dUTP nick end-labeling assay. Moreover, the P-gp function was evaluated by the intracellular accumulation of the P-gp substrate detected by flow cytometry. Results: We found the subcytotoxic doses of LA significantly enhanced adriamycin- or vincristine-induced G2/M arrest and apoptosis. These effects were consistent with the ability of LA to inhibit P-gp function. Moreover, LA dramatically enhanced the verapamil (VER) ability to reverse drug resistance. Conclusion: LA has the potential to be developed as a novel P-gp modulator. Furthermore, the combination of LA and VER might represent a more sufficient but less toxic anti-MDR regimen.

Keywords: P-glycoprotein; apoptosis; breast carcinoma; drug resistance; levistolide A

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1745-7254.2008.00719.x

Affiliations: Bio-Medical Department, East China Normal University, Shanghai 200062, China

Publication date: April 1, 2008

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Partial Open Access Content
Partial Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more