title

فعالیت ضد سرطانی انتخابی آکاسیتین بر علیه لوکمی لنفوستیک مزمن (CLL) با استفاده از روش‌های برون تنی و درون تنی: نقش کلیدی استرس اکسیداتیو و میتوکندری‌های سرطانی

سلیمی, احمد and حبیبی رودکنار, مهریار and صادقی, لیلا and محسنی, علیرضا and سیدی, عنایت اله and پیراحمدی, نهال and پوراحمد, جلال (1395) فعالیت ضد سرطانی انتخابی آکاسیتین بر علیه لوکمی لنفوستیک مزمن (CLL) با استفاده از روش‌های برون تنی و درون تنی: نقش کلیدی استرس اکسیداتیو و میتوکندری‌های سرطانی. Nutrition and Cancer ــ 68 (8). pp. 1404-1416. شاپا 0163-5581

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Title

Selective Anticancer Activity of Acacetin Against Chronic Lymphocytic Leukemia Using Both In Vivo and In Vitro Methods: Key Role of Oxidative Stress and Cancerous Mitochondria

English Abstract

The present study investigates the in vitro and in vivo effect of acacetin (4'-methoxy-5,7 dihydroxyflavone) on chronic lymphocytic leukemia (CLL) B-lymphocytes and mitochondria. CLL Blymphocytes and healthy B-lymphocytes were obtained from CLL patients and healthy donors, respectively. Mitochondria were isolated from B-lymphocytes of both groups. Xenografts in severe combined immune deficient mice were used to examine the toxicity and anti CLL activity of acacetin. We evaluated and compared the mechanism of action of acacetin on CLL and healthy Blymphocytes and their mitochondria. We have found that acacetin (10 mM) can selectively induce apoptosis on CLL B-lymphocyte (25% at 24 h) by directly targeting mitochondria, through increased reactive oxygen species (ROS) formation, MMP collapse, MPT, release of cytochrome c, caspase 3 activation, and finally apoptosis, while sparing normal healthy B-lymphocytes unaffected at similar concentrations. Besides, oral administration of acacetin showed a potent in vivo anticancer activity in CLL xenograft mouse models. Our in vivo findings indicate that acacetin accumulates and kills CLL B-lymphocyte in a rather selective way through targeting cancerous mitochondria and ROS formation, which ends in CLL therapy. Finally, we can recommend acacetin as a promising compound for further drug development assays for the CLL treatment.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :احمد سلیمی
نویسنده :مهریار حبیبی رودکنار
نویسنده :لیلا صادقی
نویسنده :علیرضا محسنی
نویسنده :عنایت اله سیدی
نویسنده :نهال پیراحمدی
نویسنده مسئول :جلال پوراحمد
Additional Information:IF: 2.447 Indexed in: ISI, PubMed/Medline, Scopus, Embase
کلیدواژه ها (انگلیسی):Chronic Lymphocytic Leukemia, Acacetin, Mitochondria, Apoptosis,Cancer
Subjects:QV pharmacology > QV 600 Toxicology
Divisions:School of Pharmacy > Department of Toxicology
ID Code:8095
Deposited By: Dr Ahmad Salimi
Deposited On:11 Sep 1395 06:19
Last Modified:25 Jan 1401 09:05

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