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International Journal of Hematology-Oncology and Stem Cell Research، جلد ۱۰، شماره ۳، صفحات ۱۲۰-۱۲۹
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عنوان انگلیسی Curcumin Veto the Effects of Osteopontin (OPN) Specific Inhibitor on Leukemic Stem Cell Colony Forming Potential via Promotion of OPN Overexpression
چکیده انگلیسی مقاله Background: Acute myeloid leukemia (AML) is an immunophenotypically heterogeneous malignant disease, in which CD34 positivity is associated with poor prognosis. Osteopontin (OPN) plays different roles in physiologic and pathologic conditions like: survival, metastasis and cell protection from cytotoxic and apoptotic stimuli. Due to anti-apoptotic effect of OPN in normal and malignant cells, silencing of OPN lead to elevation of sensitivity towards chemotherapeutic agents and attenuates cancer cells migration and invasion. Therefore, the aim of this study was to evaluate OPN roles in modulating curcumin-mediated growth inhibitory on Leukemic stem cells (LSCs) colony forming potential and survival in AML cell lines and primary CD34+/CD38- bone-marrow-derived AML cells. Materials and Methods: Primary human CD34+/CD38- cells were isolated from bone marrow mononuclear cells of 10 AML patients at initial state of diagnosis, using a CD34 Multi sort kit. The growth inhibitory effects of curcumin (CUR) were evaluated by MTT and colony-formation assays. Apoptosis was analyzed by 7AAD assay in CD34+ KG-1, U937 cell lines and primary isolated cells. Short interfering RNA (siRNA) against OPN was used for OPN silencing in both cell lines and primary AML cells. Then, transfected cells were incubated with/without curcumin. The change in OPN gene expression was examined by Real time PCR. Results: CUR inhibited proliferation and induced apoptosis in both KG-1 and U937 cells and also primary isolated AML cells.OPN silencing by siRNA increased the susceptibility of KG-1, U937 and primary CD34+/CD38- AML cells to apoptosis. Moreover, soft agar colony assays revealed that silencing of OPN with siRNA significantly decreased colony numbers in LSCs compared with the non-targeting group. Furthermore, CD34+/CD38- populations as a main LSCs compartment through OPN overexpression towards CUR treatment might be nullified the inhibitory effects of OPN siRNA on their survival and colony forming potential. Conclusion: Taken together, our results suggested that knockdown of OPN using OPN specific siRNA significantly decreased colony numbers in LSCs and this effect might be vetoed by LSCs via induction of OPN overexpressionin combination of CUR and siRNA.
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نویسندگان مقاله سعید محمدی | saeed mohammadi
iranian blood transfusion research center, high institute for education and research in transfusion medicine, tehran, iran

سازمان اصلی تایید شده: سازمان انتقال خون ایران (Blood transfusion research center)

سید h غفاری | seyed h ghaffari
hematology-oncology and stem cell transplantation research center, tehran university of medical sciences, tehran, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تهران (Tehran university of medical sciences)

مژگان شایگان | mojgan shaiegan
iranian blood transfusion research center, high institute for education and research in transfusion medicine, tehran, iran

سازمان اصلی تایید شده: سازمان انتقال خون ایران (Blood transfusion research center)

مهین نیکوگفتار ظریف | mahin nikogoftar zarif
iranian blood transfusion research center, high institute for education and research in transfusion medicine, tehran, iran

سازمان اصلی تایید شده: سازمان انتقال خون ایران (Blood transfusion research center)

محسن نیکبخت | mohsen nikbakht
hematology-oncology and stem cell transplantation research center, tehran university of medical sciences, tehran, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تهران (Tehran university of medical sciences)

کامران علی مقدم | kamran alimoghaddam
hematology-oncology and stem cell transplantation research center, tehran university of medical sciences, tehran, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تهران (Tehran university of medical sciences)

اردشیر قوام زاده | ardeshir ghavamzadeh
hematology-oncology and stem cell transplantation research center, tehran university of medical sciences, tehran, iran

سازمان اصلی تایید شده: دانشگاه علوم پزشکی تهران (Tehran university of medical sciences)

نشانی اینترنتی http://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/498
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