Apoptotic Effects of Resveratrol, a Grape Polyphenol, on Imatinib-Sensitive and Resistant K562 Chronic Myeloid Leukemia Cells

Can, Geylani
Cakir, Zeynep
Kartal, Melts
Gündüz, Ufuk
Aim: To examine the antiproliferative and apoptotic effects of resveratrol on imatinib-sensitive and imatinib-resistant K562 chronic myeloid leukemia cells. Materials and Methods: Antiproliferative effects of resveratrol were determined by the 3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxanilide inner salt (XTT) cell proliferation assay. Apoptotic effects of resveratrol on sensitive K562 and resistant K562/IMA-3 cells were determined through changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP), and apoptosis by annexin V-(FITC). Results: The concentrations of resveratrol that inhibited cell growth by 50% (IC50) were calculated as 85 and 122 mu M for K562 and K562/IMA-3 cells, respectively. There were 1.91-, 7.42- and 14.73-fold increases in loss of MMP in K562 cells treated with 10, 50, and 100 mu M resveratrol, respectively. The same concentrations of resveratrol resulted in 2.21-, 3.30- and 7.65-fold increases in loss of MMP in K562/IMA3 cells. Caspase-3 activity increased 1.04-, 2.77- and 4.8-fold in K562 and 1.02-, 1.41- and 3.46-fold in K562/IMA3 cells in response to the same concentrations of resveratrol, respectively. Apoptosis was induced in 58.7%- and 43.3% of K562 and K562/IMA-3 cells, respectively, in response to 100 mu M resveratrol. Conclusion: Taken together these results may suggest potential use of resveratrol in CML, as well as in patients with primary and/or acquired resistance to imatinib.


Targeting glucosylceramide synthase sensitizes imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulation
BARAN, YUSUF; Bielawski, Jacek; Gündüz, Ufuk; Ogretmen, Besim (2011-10-01)
Purpose Drug resistance presents a major obstacle for the treatment of some patients with chronic myeloid leukemia (CML). Pro-apoptotic ceramide mediates imatinib-induced apoptosis, and metabolism of ceramide by glucosylceramide synthase (GCS) activity, converting ceramide to glucosyl ceramide, might contribute to imatinib resistance. In this study, we investigated the role of ceramide metabolism by GCS in the regulation of imatinib-induced apoptosis in drug-sensitive and drug-resistant K562 and K562/IMA-0....
Differential gene expression analysis related to extracellular matrix components in drug-resistant RPMI-8226 cell line
Mutlu, Pelin; Gündüz, Ufuk (Elsevier BV, 2012-4)
Drug resistance remains a major obstacle to the successful use of chemotherapeutic drugs for many types of cancers including multiple myeloma. It is becoming increasingly apparent that tumor microenvironment could provide a shelter to malignant plasma cells that allow their survival after initial drug exposure. This study demonstrates alterations in gene expression levels of several extracellular matrix (ECM) components in prednisone, vincristine and melphalan-resistant RPMI-8226 myeloma cells. Resistant RP...
Expression analysis of TOP2A, MSH2 and MLH1 genes in MCF7 cells at different levels of etoposide resistance
Kaplan, Esra; Gündüz, Ufuk (2012-02-01)
Purpose: Development of resistance against anti-cancer drugs is one of the major obstacles of chemotherapy in the treatment of cancer. Etoposide is a topoisomerase II alpha (TOP2A) inhibitor, which is used in the treatment of breast cancer. Alterations in the expression of drug targets or DNA repair genes are among the important resistance mechanisms against TOP2A inhibitors. In this study, expression changes in TOP2A gene and two important mismatch repair (MMR) genes MSH2 and MLH1 were examined in order to...
Synthesis of poly (dl-lactic-co-glycolic acid) coated magnetic nanoparticles for anti-cancer drug delivery
Tansık, Gülistan; Gündüz, Ufuk; Department of Biology (2012)
One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an extern...
Effect of cobalt-60 (gamma radiation) on multidrug-resistant multiple myeloma cell lines
Mutlu, Pelin; Ural, A. Ugur; Avcu, Ferit; Dirican, Bahar; Beyzadeoglu, Murat; Gündüz, Ufuk (2011-07-01)
Emergence of resistance to chemotherapy and radiotherapy is a major obstacle for the successful treatment of MM (multiple myeloma). Prednisone, vincristine and melphalan are commonly used chemotherapeutic agents for the treatment of MM. In the current study, we examined the presence of possible cross-resistance between these drugs and gamma (gamma) radiation. Prednisone, vincristine and melphalan resistant RPMI-8226 and U-266 MM cells were generated by stepwise increasing concentrations of the drugs. The se...
Citation Formats
G. Can, Z. Cakir, M. Kartal, U. Gündüz, and Y. BARAN, “Apoptotic Effects of Resveratrol, a Grape Polyphenol, on Imatinib-Sensitive and Resistant K562 Chronic Myeloid Leukemia Cells,” ANTICANCER RESEARCH, pp. 2673–2678, 2012, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/53291.