کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8526378 | 1557944 | 2018 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Alpha, 2'-dihydroxy-4,4'-dimethoxydihydrochalcone inhibits cell proliferation, invasion, and migration in gastric cancer in part via autophagy
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کلمات کلیدی
ERKLC-3PDX3-MADCFDAN-acetyl-l-cysteinemTORNACMMPGFP3-methyladenine - 3-متیل آدنینMitogen activated protein kinase kinase - Mitogen فعال پروتئین کیناز کینازROS - ROSAutophagy - اتوفاژیIHC - ایمونوهیستوشیمیImmunohistochemistry - ایمونوهیستوشیمیTem - این استPatient derived xenograft - بیمار مبتلا به زونا زودرسlight chain 3 - زنجیره سبک 3Matrix metalloproteinases - متالوپروتئیناز ماتریکسMEK - مجاهدین خلقTransmission electron microscope - میکروسکوپ الکترونی انتقالmammalian target of rapamycin - هدف پستانداران رپامایسینextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
تومور شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Gastric cancer is a leading cause of mortality worldwide. Alpha, 2â²-dihydroxy-4,4â²-dimethoxydihydrochalcone is a type of limonoid mainly isolated from Cedrela odorata (Meliaceae) that has been shown to suppress cell proliferation in several human carcinoma cell lines. In this study, we investigated the anti-cancer ability of alpha, 2â²-dihydroxy-4,4â²-dimethoxydihydrochalcone and its underlying mechanism in MKN45 cells. Alpha, 2â²-dihydroxy-4,4â²-dimethoxydihydrochalcone induced excess reactive oxygen species (ROS) accumulation. Transwell and wound healing assays demonstrated that alpha, 2â²-dihydroxy-4,4â²-dimethoxydihydrochalcone inhibited the invasion and migration ability of MKN45 cells. Moreover, autophagy-related proteins Beclin-1, Atg5, and Atg7 were up-regulated. Light chain 3 (LC3)-I protein was converted into LC3-II under alpha, 2â²-dihydroxy-4,4â²-dimethoxydihydrochalcone exposure. Transmission electron microscopy demonstrated that alpha, 2â²-dihydroxy-4,4â²-dimethoxydihydrochalcone treatment resulted in the formation of autophagosomes. Immunofluorescence assays suggested that alpha, 2â²-dihydroxy-4,4â²-dimethoxydihydrochalcone treatment elicited dot formation of green fluorescent protein (GFP)-LC3. 3-methyladenine (3-MA), an autophagy inhibitor, demonstrated that autophagy promoted death in MKN45 cells. Western blotting showed that ROS/mitogen activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways play crucial roles in the intrinsic mechanism of alpha, 2â²-dihydroxy-4,4â²-dimethoxydihydrochalcone's activity. The combined use of N-acetyl-L-cysteine (NAC) or U0126 validated the regulatory role of ROS/MEK/ERK signaling pathways. Alpha, 2â²-dihydroxy-4,4â²-dimethoxydihydrochalcone administration inhibited the growth of MKN45 xenograft tumors in nude mice and suppressed Ki67 expression. More importantly, a similar effect was achieved in a patient-derived xenograft (PDX) model, which is more relevant to clinical application. Taken together, alpha, 2â²-dihydroxy-4,4â²-dimethoxydihydrochalcone has the potential to be further developed into an anti-tumor agent for clinical treatment of gastric cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomedicine & Pharmacotherapy - Volume 98, February 2018, Pages 709-718
Journal: Biomedicine & Pharmacotherapy - Volume 98, February 2018, Pages 709-718
نویسندگان
Boshun Wan, Junqiu Zhu, Qing Chang, Haihua Zhou, Zhan Shi, Li Min, YueJiao Cai, Honggeng Guan,