Synergism of Curcumin and Cytarabine in the Down Regulation of Multi-Drug Resistance Genes in Acute Myeloid Leukemia.
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.


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.


CONCLUSIONS
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.
Krupa
K
Shah
Sheefa
S
Mirza
Urja
U
Desai
Nayan
N
Jain
Div. of Medicinal Chemistry & Pharmacogenomics, Dept. of Cancer Biology, The Gujarat Cancer & Research Institute, NCH Campus, Asarwa, Ahmedabad-380016, Gujarat, India. rakeshmrawal@gmail.com.
Rakesh
R
Rawal
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D003561:Cytarabine / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D020394:Vault Ribonucleoprotein Particles / Q000037:antagonists & inhibitors / Q000235:genetics; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics; D000099187:Major Vault Protein
D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D003474:Curcumin; D003561:Cytarabine; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D051941:fms-Like Tyrosine Kinase 3; D000099187:Major Vault Protein; C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; C497970:FLT3 protein, human