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Novel plant triterpenoid drug amooranin overcomes multidrug resistance in human leukemia and colon carcinoma cell lines
Author(s) -
Ramachandran Cheppail,
Rabi Thangaiyan,
Fonseca Hugo B.,
Melnick Steven J.,
Escalon Enrique A.
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11180
Subject(s) - multiple drug resistance , leukemia , drug resistance , carcinoma cell , medicine , carcinoma , cancer research , cell culture , drug , biology , oncology , pharmacology , microbiology and biotechnology , genetics
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.