A Novel Resveratrol-Arsenic Trioxide Combination Treatment Synergistically Induces Apoptosis of Adriamycin-Selected Drug-Resistant Leukemia K562 Cells

In this study, we generated adriamycin-resistant K562 leukemia (K562/RA) cells and compared the responses of sensitive and resistant leukemia cells to the natural products arsenic trioxide (ATO) and resveratrol (Rsv), with a view to determining whether Rsv potentiates the sensitivity of drug-resistant cells to ATO-induced apoptosis and the associated molecular mechanisms. Our results showed that resistance of K562/RA cells induced by adriamycin treatment was significantly higher (115.81-fold) than that of parental K562 cells. Simultaneously, K562/RA cells were cross-resistant to multiple agents, with the exception of ATO. Rsv enhanced the sensitivity of K562/RA cells to ATO and reduced the required dose of ATO as well as associated adverse reactions by promoting the proliferation inhibitory and apoptosis-inducing effects of ATO, which may be associated with reduced expression of the drug resistance genes mdr1/P-gp, mrp1/MRP1 and bcrp/BCRP, as well as the apoptotic inhibitory genes bcl-2, NF-κB and P53, and conversely, activation of caspase-3. Our collective findings indicate that ATO and Rsv synergistically enhance the sensitivity of drug-resistant leukemia cells to apoptosis.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research

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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
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Source: BioImpacts - Category: Research Tags: Bioimpacts Source Type: research
Abstract Overexpression of ATP-binding cassette (ABC) transporters causing multidrug resistance (MDR) in cancer cells is one of the major obstacles in cancer chemotherapy. The 5-FU resistant subclone (HL-60/5FU) of the human HL-60 promyelocytic leukemia cell line was selected by the conventional method of continuous exposure of the cells to the drug up to 0.08 mmol/L concentration. HL-60/5FU cells exhibited six-fold enhanced resistance to 5-FU than HL-60 cells. RT-PCR and ELISA assay showed significant overexpression of MDR-related ABC transporters, ABCB1, ABCG2 but especially ABCC1 in the HL-60/5FU as compar...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research
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Source: Nutrition and Cancer - Category: Cancer & Oncology Authors: Tags: Nutr Cancer Source Type: research
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Source: Sensors and Actuators B: Chemical - Category: Chemistry Source Type: research
Authors: Kassem NM, Medhat N, Kassem HA, El-Desouky MA Abstract Background: Acute Myeloid Leukemia (AML) is a heterogeneous disorder with variable genetic abnormalities and cytogenetic alterations which provide a significant disease prognosis and determine response to therapy. Purpose: We aim to investigate the expression of the MDR1 gene in 100 Egyptian AML patients, to identify their role on both the progression and chemotherapeutic refractoriness together with assessment of known prognostic molecular markers; FLT3-ITD and NPM1 mutations. Methodology: Quantitative assessment of MDR1 gene expression was performed ...
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
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Source: Experimental Hematology - Category: Hematology Authors: Tags: 3100 Source Type: research
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Source: Experimental Hematology - Category: Hematology Authors: Tags: 3098 Source Type: research
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Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
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