Novel plant triterpenoid drug amooranin overcomes multidrug resistance in human leukemia and colon carcinoma cell lines.

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.

• 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)
• 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

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