TY - JOUR
T1 - Resveratrol-mediated reversal of doxorubicin resistance in acute myeloid leukemia cells via downregulation of MRP1 expression
AU - Kweon, Sin Ho
AU - Song, Ju Han
AU - Kim, Tae Sung
N1 - Funding Information:
This study was supported by Grants of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea ( A01-0385-A70604-07M7-00000A ) and the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MEST) ( R11-2005-017-05001-0 ).
PY - 2010/4
Y1 - 2010/4
N2 - Chemo-resistance to anti-cancer drugs is a major obstacle in efforts to develop a successful treatment of acute myeloid leukemia (AML). In this study, we investigate whether resveratrol, a common ingredient in a broad variety of fruits and vegetables, can reverse drug resistance in AML cells. Three doxorubicinresistant AML cell lines (AML-2/DX30, AML-2/DX100, AML-2/DX300) were prepared via long-term exposure to doxorubicin for more than 3 months. DNA microarray analysis demonstrated that many genes were differentially expressed in the resistant cells, as compared with the wild type AML-2/WT cells. In particular, the expression level of the MRP1 gene was significantly increased in the AML-2/DX300 cells, as compared to that detected in AML-2 cells. Importantly, the resveratrol was shown not only to induce cell growth arrest and apoptotic death in doxorubicin-resistant AML cells, but was also shown to downregulate the expression of an MRP1 gene. Furthermore, resveratrol treatment induced a significant increase in the uptake of 5(6)-carboxyfluorescein diacetate, a MRP1 substrate, into the doxorubicin-resistant AML-2/DX300 cells. The results of this study show that resveratrol may facilitate the cellular uptake of doxorubicin via an induced downregulation of MRP1 expression, and also suggest that it may prove useful in overcoming doxorubicin resistance, or in sensitizing doxorubicin-resistant AML cells to anti-leukemic agents.
AB - Chemo-resistance to anti-cancer drugs is a major obstacle in efforts to develop a successful treatment of acute myeloid leukemia (AML). In this study, we investigate whether resveratrol, a common ingredient in a broad variety of fruits and vegetables, can reverse drug resistance in AML cells. Three doxorubicinresistant AML cell lines (AML-2/DX30, AML-2/DX100, AML-2/DX300) were prepared via long-term exposure to doxorubicin for more than 3 months. DNA microarray analysis demonstrated that many genes were differentially expressed in the resistant cells, as compared with the wild type AML-2/WT cells. In particular, the expression level of the MRP1 gene was significantly increased in the AML-2/DX300 cells, as compared to that detected in AML-2 cells. Importantly, the resveratrol was shown not only to induce cell growth arrest and apoptotic death in doxorubicin-resistant AML cells, but was also shown to downregulate the expression of an MRP1 gene. Furthermore, resveratrol treatment induced a significant increase in the uptake of 5(6)-carboxyfluorescein diacetate, a MRP1 substrate, into the doxorubicin-resistant AML-2/DX300 cells. The results of this study show that resveratrol may facilitate the cellular uptake of doxorubicin via an induced downregulation of MRP1 expression, and also suggest that it may prove useful in overcoming doxorubicin resistance, or in sensitizing doxorubicin-resistant AML cells to anti-leukemic agents.
KW - Acute myeloid leukemia
KW - Doxorubicin
KW - Drug resistance
KW - MRP1
KW - Resveratrol
UR - http://www.scopus.com/inward/record.url?scp=77951934363&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2010.03.147
DO - 10.1016/j.bbrc.2010.03.147
M3 - Article
C2 - 20350534
AN - SCOPUS:77951934363
SN - 0006-291X
VL - 395
SP - 104
EP - 110
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -
