Berberine potently attenuates intestinal polyps growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling

Abstract

As a traditional anti-inflammatory Chinese herbal medicine, Alkaloid berberine has been recently reported to exhibit anti-tumour effects against a wide spectrum of cancer. However, the mechanism was largely unknown. Gene chip array reveals that with berberine treatment, c-Myc, the target gene of Wnt pathway, was down-regulated 5.3-folds, indicating that berberine might inhibit Wnt signalling. TOPflash analysis revealed that Wnt activity was significantly reduced after berberine treatment, and the mechanism of which might be that berberine disrupted β-catenin transfer to nucleus through up-regulating the expression of adenomatous polyposis coli (APC) gene and stabilized APC-β-catenin complex. Berberine administration in ApcMin/+ mice exhibited fewer and smaller polyps in intestine, along with reduction in cyclin D1 and c-Myc expression. In clinical practice, oral administration of berberine also significantly reduced the familial adenomatous polyposis patients' polyp size along with the inhibition of cyclin D1 expression in polyp samples. These observations indicate that berberine inhibits colon tumour formation through inhibition of Wnt/β-catenin signalling and berberine might be a promising drug for the prevention of colon cancer.

Isoquinoline Alkaloid Berberine Exerts its Antineoplastic Activity by Inducing Molecular DNA Damage in HeLa Cells: A Comet Assay Study

“…A concentration dependent decline in the cell survival has been observed in various prostate cancer cells treated with berberine [37]. A similar effect has been observed earlier in SNU-5, human glioblastomaT98G and colon cancer KM12C, KM12SM and KM12L4A cells treated with berberine [38][39][40][41]. Berberine has been shown to induce DNA damage in Ehrlich ascites carcinoma cells [19].…”

Ellagic acid regulates Wnt/β-catenin signaling pathway and CDK8 in HCT 116 and HT 29 colon cancer cells

“…Studies have demonstrated that phytochemicals are effective in modulating Wnt/ -catenin signalling pathway (Zhang, et al, 2013;Kim et al, 2014). Ellagic acid, a dimeric derivative of gallic acid occurs naturally in fruits as-strawberry, raspberry, pomegranate, grapes and blackberries and in nuts (Thresiamma and Kuttan, 1996;Talcott and Lee, 2002;Mullen et al, 2003).…”

“…Genetic defects triggering aberrant activation of Wnt/ -catenin signalling are common and are reported in over 90% of sporadic cases of colon cancer (Miyaki et al, 1994;Clevers, 2006;Klaus and Birchmeier, 2008;Schon et al, 2014). The key effecttor of Wnt/ -catenin signaling pathway is -catenin that upon activation of Wnt signal, translocates into the nuclear region forming a ternary complex with transcription factors-TCF/Lef (T-cell factor, lymphoid enhancer factor) and activates genes involved in cell pro- Studies have demonstrated that phytochemicals are effective in modulating Wnt/ -catenin signalling pathway (Zhang, et al, 2013;Kim et al, 2014). Ellagic acid, a dimeric derivative of gallic acid occurs naturally in fruits as-strawberry, raspberry, pomegranate, grapes and blackberries and in nuts (Thresiamma and Kuttan, 1996;Talcott and Lee, 2002;Mullen et al, 2003).…”

Pretreatment with a combination of ligustrazine and berberine improves cardiac function in rats with coronary microembolization

“…Both ligustrazine and berberine are the component of Chinese herbs that have been used for more than two decades for the treatment of atherosclerotic and inflammatory diseases [26][27][28][29] . Our study demonstrated that ligustrazine alone improved cardiac function in CME rats, as evidenced by an increased +dp/dt max , decreased LVEDP, and decreased serum CK-MB level.…”