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Anti-proliferative activity and suppression of P-glycoprotein by (-)-antofine, a natural phenanthroindolizidine alkaloid, in paclitaxel-resistant human lung cancer cells

Title
Anti-proliferative activity and suppression of P-glycoprotein by (-)-antofine, a natural phenanthroindolizidine alkaloid, in paclitaxel-resistant human lung cancer cells
Authors
Kim E.-H.Min H.-Y.Chung H.-J.Song J.Park H.-J.Kim S.Lee S.K.
Ewha Authors
이상국
Issue Date
2012
Journal Title
Food and Chemical Toxicology
ISSN
0278-6915JCR Link
Citation
vol. 50, no. 41337, pp. 1060 - 1065
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Multidrug resistance (MDR) is a major obstacle in effective chemotherapy for cancer patients. The expression of P-glycoprotein (P-gp) in cancer cells is highly correlated with resistance to chemotherapeutic drugs. (-)-Antofine, a phenanthroindolizidine alkaloid derived from Cynanchum paniculatum, inhibits the growth of various human cancer cells. In this study, we further explored the potential of (-)-antofine to overcome the resistance induced by anti-cancer drugs. To this end, we established the paclitaxel-resistant human lung cancer cell line A549-PA by gradually exposing A549 cells to increasing concentrations of paclitaxel. As a result, the A549-PA cells acquired resistance against paclitaxel treatment and had an IC 50 that was more than 200 times that of the parental A549 cells. (-)-Antofine, however, effectively suppressed the growth of both the parental and drug-resistant cells. Additional studies revealed that the anti-proliferative activity of (-)-antofine in A549-PA cells is accompanied by a down-regulation of P-gp mRNA and protein expression. The effect of reversing the multidrug resistance of A549-PA cells via (-)-antofine treatment was demonstrated an increase in intracellular rhodamine-123 accumulation, measured using FACS analysis. These findings suggest an additional chemotherapeutic value of (-)-antofine, that is, regulation of cancer cell drug resistance, in addition to its antitumor effect. © 2011 Elsevier Ltd.
DOI
10.1016/j.fct.2011.11.008
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약학대학 > 약학과 > Journal papers
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