Drug Resistant MCF-7 Cell Lines Also Developed Cross-Resistance to Structurally Unrelated Anticancer Agents

Iseri, Ozlem D.
Kars, Meltem D.
Eroglu, Seckin
Gündüz, Ufuk
The cells developing resistance to an applied drug may also present cross-resistance to other anticancer drugs which are not applied. In this study, the development of cross-resistance in paclitaxel (MCF-7/Pac), docetaxel (MCF-7/Doc), vincristine (MCF-7/Vinc) and doxorubicin (MCF-7/Dox) resistant MCF-7 cells to selective anticancer drugs, tamoxifen and all trans-retinoic acid (ATRA) were investigated. Combined antiproliferative effects of these drugs in different combinations were also evaluated by checkerboard combination assay. MCF-7/Pac and MCF-7/Doc cells developed cross-resistance to vincristine (13- and 12-folds, respectively) and tamoxifen (3- and 2-folds, respectively). MCF-7/Dox cells developed cross-resistance to paclitaxel (109-fold), docetaxel (10-fold), tamoxifen (2-fold) and ATRA (3-fold). MCF-7/Vinc cells developed cross-resistance to paclitaxel (48-fold), doxorubicin (6-fold) and tamoxifen (2-fold). Combinations of paclitaxel and docetaxel with doxorubicin exerted synergic anti proliferative effect. Tamoxifen had synergic effect with doxorubicin and vincristine. ATRA had indifferent effect with paclitaxel, docetaxel and doxorubicin where it had antagonistic effect with vincristine. The data presented here may provide an insight to assess response of breast tumors to anticancer drug combinations.


Reversal of multidrug resistance in mcf-7 breast adenocarcinoma cell line by silencing interleukin 6 with RNA interference
Çakmak, Neşe; Gündüz, Ufuk; Department of Biology (2013)
Multidrug resistance (MDR) in cancer is characterized by development of resistance to several unrelated drugs upon long time administration of a certain type of chemotherapeutic agent. In doxorubicin resistant MCF-7 cell line, resistance is developed mainly by upregulation of MDR1 gene which encodes an ABC transporter protein known as P-glycoprotein. Interleukin 6 (IL-6) is a cytokine which acts as a growth factor for certain cell types including some cancer cells. IL-6 is found at high levels in cancer pat...
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...
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....
Different Types of Cell Cycle- and Apoptosis-Related Gene Expressions Alter in Corticosteroid-, Vincristine-, and Melphalan-Resistant U-266 Multiple Myeloma Cell Lines
Mutlu, Pelin; Gündüz, Ufuk (2014-09-01)
Objective: Deregulation of the cell cycle and apoptosis mechanisms in normal cells causes many problems, including cancer. In this study, a genome-wide expression analysis of cell cycle- and apoptosis-related genes in corticosteroid-, vincristine-, and melphalan-resistant U-266 multiple myeloma cell lines was conducted.
Protein kinase D2 silencing reduced motility of doxorubicin-resistant MCF7 cells
Alpsoy, Aktan; Gündüz, Ufuk (2015-06-01)
Success of chemotherapy is generally impaired by multidrug resistance, intrinsic resistance, or acquired resistance to functionally and structurally irrelevant drugs. Multidrug resistance emerges via distinct mechanisms: increased drug export, decreased drug internalization, dysfunctional apoptotic machinery, increased DNA damage repair, altered cell cycle regulation, and increased drug detoxification. Several reports demonstrated that multidrug resistance is a multifaceted problem such that multidrug resis...
Citation Formats
O. D. Iseri, M. D. Kars, S. Eroglu, and U. Gündüz, “Drug Resistant MCF-7 Cell Lines Also Developed Cross-Resistance to Structurally Unrelated Anticancer Agents,” UHOD-ULUSLARARASI HEMATOLOJI-ONKOLOJI DERGISI, pp. 1–8, 2009, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/55299.