Journal of Iranian Blood Transfusion

fa القای مرگ سلولی و کاهش تکثیر در سلول لوسمی پرومیلوسیتیک حاد NB4 توسط کافئین Induction of cell death and decreased cell proliferation in acute promyelocytic leukemia cells (NB4) by caffeine خون و انكولوژي Hematology and Oncology پژوهشي Research چکیده سابقه و هدف پیشگیری، درمان و کنترل سرطان با استفاده از مواد طبیعی در حال حاضر به عنوان یک استراتژی امیدوارکننده در نظر گرفته شده است. در این خصوص، کافئین که یک آلکالوئید پورینی موجود در گیاهان مختلف از جمله قهوه، کاکائو، کولا و چای می‌باشد، به دلیل مهار چند منظوره سرطان از جمله لوسمی‌ها به تازگی توجه زیادی به خود جلب کرده است. مواد و روش‌ها در یک مطالعه تجربی به منظور بررسی اثر کافئین در لوسمی پرومیلوسیتیک حاد، سلول‌های NB4 در غلظت‌های 1، 2 و 4 میلی مولار کافئین کشت داده شد و متعاقباً از آزمون‌های MTT ،Caspase 3 ،BrdU cell proliferation assay و Quantitative Real-Time PCR جهت بررسی اثر کافئین در القای مرگ سلولی و مطالعه مکانیسم احتمالی آن استفاده شد. آزمون paired student t test و نرم‌افزار 16 SPSS جهت تحلیل داده‌ها به کار رفت. یافته‌ها بررسی میزان ساخت DNA و بقای سلولی با استفاده از روش‌های BrdU و MTT، نشان داد که کافئین میزان تکثیر و بقای سلوهای NB4 را به صورت وابسته به دوز و زمان کاهش می‌دهد. هم چنین نتایج به دست آمده از این تحقیق نشان داد که افزایش دوز کافئین موجب القای فعال شدن آنزیم کاسپاز 3 و افزایش بیان mRNA ژن Bax و p21 می‌گردد. نتیجه گیری در مجموع، با توجه به این که مشخص شد کافئین می‌تواند موجب مهار تکثیر و القای آپوپتوز در سلول‌های لوسمی پرومیلوسیتیک حاد NB4 شود، لذا می‌توان چنین نتیجه‌گیری کرد که مصرف کافئین به عنوان ماده‌ای در چای ممکن است یک عامل مفید جهت القای مرگ سلولی این سلول‌های بدخیم در مبتلایان به لوسمی پرومیلوسیتیک حاد عمل کند. Abstract Background and Objectives Prevention, control and treatment of cancer using natural materials currently have been considered as the promising strategy. In this regard, caffeine as a purine alkaloid found in various plants, including coffee, cocoa, cola and tea has recently attracted great interest because of its remarkable multifunctional inhibitory effects on cancers such as leukemia. Regarding the anti-cancer effects of caffeine, we sought to investigate the effectiveness of this methylxanthine alkaloid against NB4 acute promyelocytic leukemia cells. Materials and Methods In order to examine the effects of caffeine in APL, NB4 cells were cultured in the presence of different concentrations of caffeine subsequently, MTT, Caspase 3 activity assay, BrdU cell proliferation assay and quantitative real-time PCR were performed to assess the effect of caffeine on cell viability and the possible mechanisms of inducing cell death. Results Evaluation of DNA synthesis and cell survival using BrdU and MTT methods indicated that caffeine reduces proliferation and survival of NB4 cells in a dose and time dependent manner. The results of this study showed that elevation in the dose of caffeine induces caspase-3 activation and increases Bax and p21 gene mRNA expression levels. Conclusions Overall, our data illustrate that caffeine inhibits cell proliferation and induces apoptosis in acute promyelocytic leukemia NB4 cells. Thus, it can be concluded that caffeine as a substance in tea may be a useful agent for induction of cell death in malignant cells of patients with acute promyelocytic leukemia. Key words: Acute Promyelocytic Leukemia, Apoptosis, Caffeine, Caspases Abstract Background and Objectives Prevention, control and treatment of cancer using natural materials currently have been considered as the promising strategy. In this regard, caffeine as a purine alkaloid found in various plants, including coffee, cocoa, cola and tea has recently attracted great interest because of its remarkable multifunctional inhibitory effects on cancers such as leukemia. Regarding the anti-cancer effects of caffeine, we sought to investigate the effectiveness of this methylxanthine alkaloid against NB4 acute promyelocytic leukemia cells. Materials and Methods In order to examine the effects of caffeine in APL, NB4 cells were cultured in the presence of different concentrations of caffeine subsequently, MTT, Caspase 3 activity assay, BrdU cell proliferation assay and quantitative real-time PCR were performed to assess the effect of caffeine on cell viability and the possible mechanisms of inducing cell death. Results Evaluation of DNA synthesis and cell survival using BrdU and MTT methods indicated that caffeine reduces proliferation and survival of NB4 cells in a dose and time dependent manner. The results of this study showed that elevation in the dose of caffeine induces caspase-3 activation and increases Bax and p21 gene mRNA expression levels. Conclusions Overall, our data illustrate that caffeine inhibits cell proliferation and induces apoptosis in acute promyelocytic leukemia NB4 cells. Thus, it can be concluded that caffeine as a substance in tea may be a useful agent for induction of cell death in malignant cells of patients with acute promyelocytic leukemia. Key words: Acute Promyelocytic Leukemia, Apoptosis, Caffeine, Caspases Abstract Background and Objectives Prevention, control and treatment of cancer using natural materials currently have been considered as the promising strategy. In this regard, caffeine as a purine alkaloid found in various plants, including coffee, cocoa, cola and tea has recently attracted great interest because of its remarkable multifunctional inhibitory effects on cancers such as leukemia. Regarding the anti-cancer effects of caffeine, we sought to investigate the effectiveness of this methylxanthine alkaloid against NB4 acute promyelocytic leukemia cells. Materials and Methods In order to examine the effects of caffeine in APL, NB4 cells were cultured in the presence of different concentrations of caffeine subsequently, MTT, Caspase 3 activity assay, BrdU cell proliferation assay and quantitative real-time PCR were performed to assess the effect of caffeine on cell viability and the possible mechanisms of inducing cell death. Results Evaluation of DNA synthesis and cell survival using BrdU and MTT methods indicated that caffeine reduces proliferation and survival of NB4 cells in a dose and time dependent manner. The results of this study showed that elevation in the dose of caffeine induces caspase-3 activation and increases Bax and p21 gene mRNA expression levels. Conclusions Overall, our data illustrate that caffeine inhibits cell proliferation and induces apoptosis in acute promyelocytic leukemia NB4 cells. Thus, it can be concluded that caffeine as a substance in tea may be a useful agent for induction of cell death in malignant cells of patients with acute promyelocytic leukemia. لوسمی پرومیلوسیتیک حاد, آپوپتوز, کافئین, کاسپاز Key words: Acute Promyelocytic Leukemia, Apoptosis, Caffeine, Caspases 331 339 http://bloodjournal.ir/browse.php?a_code=A-10-526-2&slc_lang=fa&sid=1 M. Safa مجید صفا m-safa@tums.ac.ir 9100319475328460013316 9100319475328460013316 Yes تهران ـ ایران ـ صندوق پستی: 63113-19839 D. Bashash داود بشاش David_5980@yahoo.com 9100319475328460013317 9100319475328460013317 No تهران ـ ایران ـ کدپستی: 1971653312 M. Hamidpoor محسن حمیدپور mohsenhp@sbmu.ac.ir 9100319475328460013318 9100319475328460013318 No گروه هماتولوژی، دانشکده پیراپزشکی، دانشگاه علوم پزشکی شهید بهشتی