Anti-cancer agents in medicinal chemistry · 2016
Synergism of Curcumin and Cytarabine in the Down Regulation of Multi-Drug Resistance Genes in Acute Myeloid Leukemia.
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Shah Krupa, Mirza Sheefa, Desai Urja, Jain Nayan, Rawal Rakesh
Аннотация
BACKGROUND: The aim of the study was to find a role of Curcumin from natural source to overcome drug resistance as well as to reduce cytotoxicity profile of the drug in Acute Myeloid Leukemia patients.
MATERIAL AND METHODS: Primary leukemic cells were obtained from AML patient's bone marrow. These cells were then exposed to different concentration of cytarabine and curcumin to find out IC50 values and also its effect on MDR genes like MDR1, BCRP, LRP and FLT3 by RT-PCR method.
RESULT & CONCLUSION: Our results suggested that curcumin down regulates MDR genes. Gene expression was decreased by 35.75, 31.30, 27.97 % for MDR1, LRP, BCRP respectively. In FLT3, it was 65.86 % for wild type and 31.79 % for FLT3-ITD. In addition to this, curcumin has also shown anti-proliferative effect as well as synergistic effect in combination with Cytarabine on primary leukemic cells. Thus, we can conclude that curcumin can be used as MDR modulator as well as chemosensitizer in combination with cytarabine, standard chemotherapeutic drug, to reduce the cytotoxicity profile as IC50 value decreases when treated in combination.
MATERIAL AND METHODS: Primary leukemic cells were obtained from AML patient's bone marrow. These cells were then exposed to different concentration of cytarabine and curcumin to find out IC50 values and also its effect on MDR genes like MDR1, BCRP, LRP and FLT3 by RT-PCR method.
RESULT & CONCLUSION: Our results suggested that curcumin down regulates MDR genes. Gene expression was decreased by 35.75, 31.30, 27.97 % for MDR1, LRP, BCRP respectively. In FLT3, it was 65.86 % for wild type and 31.79 % for FLT3-ITD. In addition to this, curcumin has also shown anti-proliferative effect as well as synergistic effect in combination with Cytarabine on primary leukemic cells. Thus, we can conclude that curcumin can be used as MDR modulator as well as chemosensitizer in combination with cytarabine, standard chemotherapeutic drug, to reduce the cytotoxicity profile as IC50 value decreases when treated in combination.
Предметные рубрики MeSH
ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2ATP-Binding Cassette TransportersAntineoplastic AgentsCell Line, TumorCell ProliferationCell SurvivalCurcuminCytarabineDose-Response Relationship, DrugDown-RegulationDrug Resistance, MultipleDrug Resistance, NeoplasmDrug Screening Assays, AntitumorDrug SynergismHumansLeukemia, Myeloid, AcuteNeoplasm ProteinsReal-Time Polymerase Chain ReactionStructure-Activity RelationshipVault Ribonucleoprotein Particlesfms-Like Tyrosine Kinase 3Major Vault Protein