دورية أكاديمية
أعرض في EDS

Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice.

التفاصيل البيبلوغرافية
العنوان: Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice.
المؤلفون: Li W; Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland.; Oncology Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China., Hua B; Oncology Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China., Saud SM; Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland., Lin H; Oncology Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China., Hou W; Oncology Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China., Matter MS; Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Jia L; Office of Cancer Complementary and Alternative Medicine, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Rockville, Maryland., Colburn NH; Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland., Young MR; Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland.
المصدر: Molecular carcinogenesis [Mol Carcinog] 2015 Oct; Vol. 54 (10), pp. 1096-109. Date of Electronic Publication: 2014 May 17.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8811105 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-2744 (Electronic) Linking ISSN: 08991987 NLM ISO Abbreviation: Mol Carcinog Subsets: MEDLINE
أسماء مطبوعة: Publication: <2005- > : [Hoboken, N.J.] : Wiley-Liss
Original Publication: New York : Alan R. Liss, Inc., c1988-
مواضيع طبية MeSH: AMP-Activated Protein Kinases/*metabolism , Berberine/*pharmacology , Carcinogenesis/*drug effects , Colon/*drug effects , Colorectal Neoplasms/*drug therapy , Signal Transduction/*drug effects, Animals ; Apoptosis/drug effects ; Azoxymethane/pharmacology ; Carcinogenesis/metabolism ; Carcinogenesis/pathology ; Caspase 3/metabolism ; Cell Line, Tumor ; Colon/metabolism ; Colon/pathology ; Colorectal Neoplasms/metabolism ; Cyclin D1/metabolism ; Cyclooxygenase 2/metabolism ; Female ; HCT116 Cells ; Humans ; Mice ; NF-kappa B/metabolism ; Phosphorylation/drug effects ; Protein Serine-Threonine Kinases/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Tumor Suppressor Protein p53/metabolism ; eIF-2 Kinase/metabolism
مستخلص: Colorectal cancer, a leading cause of cancer death, has been linked to inflammation and obesity. Berberine, an isoquinoline alkaloid, possesses anti-inflammatory, anti-diabetes and anti-tumor properties. In the azoxymethane initiated and dextran sulfate sodium (AOM/DSS) promoted colorectal carcinogenesis mouse model, berberine treated mice showed a 60% reduction in tumor number (P = 0.009), a 48% reduction in tumors <2 mm, (P = 0.05); 94% reduction in tumors 2-4 mm, (P = 0.001), and 100% reduction in tumors >4 mm (P = 0.02) compared to vehicle treated mice. Berberine also decreased AOM/DSS induced Ki-67 and COX-2 expression. In vitro analysis showed that in addition to its anti-proliferation activity, berberine also induced apoptosis in colorectal cancer cell lines. Berberine activated AMP-activated protein kinase (AMPK), a major regulator of metabolic pathways, and inhibited mammalian target of rapamycin (mTOR), a downstream target of AMPK. Furthermore, 4E-binding protein-1 and p70 ribosomal S6 kinases, downstream targets of mTOR, were down regulated by berberine treatment. Berberine did not affect Liver kinase B1 (LKB1) activity or the mitogen-activated protein kinase pathway. Berberine inhibited Nuclear Factor kappa-B (NF-κB) activity, reduced the expression of cyclin D1 and survivin, induced phosphorylation of p53 and increased caspase-3 cleavage in vitro. Berberine inhibition of mTOR activity and p53 phosphorylation was found to be AMPK dependent, while inhibition NF-κB was AMPK independent. In vivo, berberine also activated AMPK, inhibited mTOR and p65 phosphorylation and activated caspase-3 cleavage. Our data suggests that berberine suppresses colon epithelial proliferation and tumorigenesis via AMPK dependent inhibition of mTOR activity and AMPK independent inhibition of NF-κB.
(© 2014 Wiley Periodicals, Inc.)
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معلومات مُعتمدة: Z99 CA999999 United States Intramural NIH HHS; ZIA BC011159 United States Intramural NIH HHS
فهرسة مساهمة: Keywords: AMP-activated protein kinase; berberine; colorectal cancer treatment; mammalian target of rapamycin; prevention; proliferation
المشرفين على المادة: 0 (NF-kappa B)
0 (Tumor Suppressor Protein p53)
0I8Y3P32UF (Berberine)
136601-57-5 (Cyclin D1)
EC 1.14.99.1 (Cyclooxygenase 2)
EC 2.7.1.1 (MTOR protein, human)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
EC 2.7.11.1 (eIF-2 Kinase)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
EC 3.4.22.- (Caspase 3)
MO0N1J0SEN (Azoxymethane)
تواريخ الأحداث: Date Created: 20140520 Date Completed: 20151207 Latest Revision: 20211203
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4504840
DOI: 10.1002/mc.22179
PMID: 24838344
قاعدة البيانات: MEDLINE
الوصف
تدمد:1098-2744
DOI:10.1002/mc.22179