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Berberine, an isoquinoline alkaloid, possesses anti\u2010inflammatory, anti\u2010diabetes and anti\u2010tumor 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 (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.009), a 48% reduction in tumors &lt;2\u2009mm, (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.05); 94% reduction in tumors 2\u20134\u2009mm, (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.001), and 100% reduction in tumors &gt;4\u2009mm (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.02) compared to vehicle treated mice. Berberine also decreased AOM\/DSS induced Ki\u201067 and COX\u20102 expression. In vitro analysis showed that in addition to its anti\u2010proliferation activity, berberine also induced apoptosis in colorectal cancer cell lines. Berberine activated AMP\u2010activated protein kinase (AMPK), a major regulator of metabolic pathways, and inhibited mammalian target of rapamycin (mTOR), a downstream target of AMPK. Furthermore, 4E\u2010binding protein\u20101 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\u2010activated protein kinase pathway. Berberine inhibited Nuclear Factor kappa\u2010B (NF\u2010\u03baB) activity, reduced the expression of cyclin D1 and survivin, induced phosphorylation of p53 and increased caspase\u20103 cleavage in vitro. Berberine inhibition of mTOR activity and p53 phosphorylation was found to be AMPK dependent, while inhibition NF\u2010\u03baB was AMPK independent. In vivo, berberine also activated AMPK, inhibited mTOR and p65 phosphorylation and activated caspase\u20103 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\u2010\u03baB. \u00a9 2014 Wiley Periodicals, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mc.22179","type":"journal-article","created":{"date-parts":[[2014,5,17]],"date-time":"2014-05-17T12:27:42Z","timestamp":1400329662000},"page":"1096-1109","source":"Crossref","is-referenced-by-count":121,"title":["Berberine regulates AMP\u2010activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice"],"prefix":"10.1002","volume":"54","author":[{"given":"Weidong","family":"Li","sequence":"first","affiliation":[{"name":"Laboratory of Cancer Prevention Center for Cancer Research National Cancer Institute National Institutes of Health Frederick Maryland"},{"name":"Oncology Department Guang'anmen Hospital China Academy of Chinese Medical Sciences Beijing 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