کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5509274 | 1538504 | 2017 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Metformin triggers apoptosis in PEL cells and alters bortezomib-induced Unfolded Protein Response increasing its cytotoxicity and inhibiting KSHV lytic cycle activation
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کلمات کلیدی
AMPKLC3IRE1UPRATF64E-BP1KSHVLANABAFmTORATF4STAT3AMP-activated protein kinase - AMP-پروتئین کیناز فعال شده استC/EBP-homologous protein - C / EBP-homologous proteinER-stress - ER-استرسROS - ROSinositol-requiring enzyme 1 - آنزیم مورد نیاز inositol 1Autophagy - اتوفاژیPEL - از PELER stress - استرس استEndoplasmic reticulum stress - استرس شبکه آندوپلاسمیbafilomycin A1 - بافیلومایسین A1Bortezomib - بورتِـزومیبCHOP - تکه کردنactivating transcription factor 4 - فعال کردن عامل رونویسی 4activating transcription factor 6 - فعال کردن عامل رونویسی 6Primary effusion lymphoma - لنفوم اپوژن اولیهsignal transducer and activator of transcription 3 - مبدل سیگنال و فعال کننده رونویسی 3Metformin - متفورمینMET - ملاقات کردmammalian target of rapamycin - هدف پستانداران رپامایسینKaposi's sarcoma-associated herpesvirus - ویروسهای مرتبط با سارکوم کاپوزیUnfolded protein response - پاسخ پروتئین آشکارmicrotubule-associated protein 1A/1B-light chain 3 - پروتئین پروتئین 1A / 1B مرتبط با میکروتوبول زنجیره 3Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Metformin triggers apoptosis in PEL cells and alters bortezomib-induced Unfolded Protein Response increasing its cytotoxicity and inhibiting KSHV lytic cycle activation Metformin triggers apoptosis in PEL cells and alters bortezomib-induced Unfolded Protein Response increasing its cytotoxicity and inhibiting KSHV lytic cycle activation](/preview/png/5509274.png)
چکیده انگلیسی
Metformin, the most used drug for the treatment of diabetes type 2 patients, has been shown to have anti-cancer properties. In this study, we found that metformin induced apoptosis in Primary Effusion Lymphoma (PEL) cells, an aggressive B cell lymphoma associated with KSHV against which the conventional therapies usually fail. The cytotoxic effect of metformin correlated with intracellular reactive oxygen species reduction, activation of AMPK, the inhibition of pro-survival pathways such as mTOR and STAT3 and the down-regulation of v-FLIP, a latent viral antigen that also plays a pivotal role in PEL cell survival. Interestingly, we found that metformin could be used to potentiate the bortezomib-mediated cytotoxicity against PEL cells and to inhibit the activation of KSHV lytic cycle, a side effect of this treatment that resulted in a block of autophagy in these cells. Mechanistically, metformin altered UPR activated by bortezomib, leading to a reduced expression of BiP, up-regulation of CHOP and down-regulation of Bcl-2. In summary, this study suggests that metformin could represent a promising strategy for the treatment of PEL alone or in combination with bortezomib. In the latter case, besides exerting a stronger cytotoxic effect, it might be used to restrain bortezomib-induced viral replication that is involved in the maintenance and progression of KSHV-associated malignancies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 40, December 2017, Pages 239-247
Journal: Cellular Signalling - Volume 40, December 2017, Pages 239-247
نویسندگان
Marisa Granato, Maria Saveria Gilardini Montani, Maria Anele Romeo, Roberta Santarelli, Roberta Gonnella, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone,