Novel plant triterpenoid drug amooranin overcomes multidrug resistance in human leukemia and colon carcinoma cell lines
✍ Scribed by Cheppail Ramachandran; Thangaiyan Rabi; Hugo B. Fonseca; Steven J. Melnick; Enrique A. Escalon
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- French
- Weight
- 186 KB
- Volume
- 105
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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. © 2003 Wiley‐Liss, Inc.