Abstract |
Amooranin (AMR), a plant terpenoid, isolated from Amoora rohituka, was investigated for its ability to overcome multidrug resistance in human leukemia and colon carcinoma cell lines. AMR IC(50) values of multidrug-resistant leukemia (CEM/VLB) and colon carcinoma (SW620/Ad-300) cell lines were higher (1.9- and 6-fold) than parental sensitive cell lines (CEM and SW620). AMR induced G(2)+M phase-arrest during cell cycle traverse in leukemia and colon carcinoma cell lines and the percentage of cells in G(2)+M phase increased in a dose-dependent manner. Coincubation of tumor cells with both DOX and AMR reversed DOX resistance in 104-fold DOX-resistant CEM/VLB and 111-fold DOX-resistant SW620/Ad-300 cell lines with a dose modification factor of 50.9 and 99.6, respectively. Flow cytometric assay showed that AMR causes enhanced cellular DOX accumulation in a dose-dependent manner. AMR inhibits photolabeling of P-glycoprotein (P-gp) with [(3)H]- azidopine and the blocking effect enhanced with increasing concentrations of AMR. Our results show that AMR competitively inhibits P-gp-mediated DOX efflux, suggestive of a mechanism underlying the enhanced DOX accumulation and reversal of multidrug resistance by AMR.
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Authors | Cheppail Ramachandran, Thangaiyan Rabi, Hugo B Fonseca, Steven J Melnick, Enrique A Escalon |
Journal | International journal of cancer
(Int J Cancer)
Vol. 105
Issue 6
Pg. 784-9
(Jul 20 2003)
ISSN: 0020-7136 [Print] United States |
PMID | 12767063
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2003 Wiley-Liss, Inc. |
Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Affinity Labels
- Antineoplastic Agents, Phytogenic
- Azides
- Dihydropyridines
- Triterpenes
- amooranin
- azidopine
- Doxorubicin
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(analysis)
- Affinity Labels
- Antineoplastic Agents, Phytogenic
(chemistry, toxicity)
- Azides
- Carcinoma
(drug therapy, metabolism)
- Cell Cycle
(drug effects)
- Cell Survival
(drug effects)
- Colonic Neoplasms
(drug therapy, metabolism)
- Dihydropyridines
- Dose-Response Relationship, Drug
- Doxorubicin
(metabolism, toxicity)
- Drug Resistance, Multiple
- Drug Resistance, Neoplasm
- Humans
- Leukemia
(drug therapy, metabolism)
- Triterpenes
(chemistry, toxicity)
- Tumor Cells, Cultured
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