Berberine: A potential adjunct for the treatment of gastrointestinal cancers?

Abstract

Gastrointestinal cancers are among the most prevalent cancers in the general population. Despite effective early diagnostics and intervention, the gastrointestinal cancer-related mortality still remains elevated. Berberine (BBR) is a benzyl tetra isoquinoline alkaloid exracted from several plants. BBR is nontoxic to human normal cells, but suppresses the growth of different tumor cells: melanoma, epidermoid carcinoma, hepatoma, oral carcinoma, glioblastoma, prostatic carcinoma, and gastric carcinoma. In particular, BBR seems to suppress the proliferation of gastrointestinal cancers in a number of preclinical models. Several mechanisms of action have been hypothesized and demonstrated: immunomodulation, inhibition of topoisomerase enzymes, suppression of the EGF receptor, Her2/neu, and the VEGF receptor, induction of p53, Cip1/p21, Kip1/p27, Rb expression, induction of apoptosis (by regulation of MMPs pathway, caspases, Bax, and Smac/DIABLO), inhibition of arylamin N-acetyltransferase activity, and regulation of microRNAs expression. The aim of this review is to summarize the pharmacological effects of BBR on animal and human gastrointestinal cancers.

Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice

“…(Berberidaceae) has long been a part of traditional Chinese and Ayurvedic medicine. Preclinical efficacy of berberine has been established in various cancers including colon , breast (Zhao et al, 2017), gastrointestinal (Hesari et al, 2018), oral , liver (Tsang et al, 2015), pancreas (Abrams et al, 2019), prostate (Youn et al, 2018), ovarian (Hou et al, 2017), and cervical (Mahata et al, 2011) cancers. Despite large preclinical efficacy data, clinical trials related to the evaluation of true potential of berberine as an anticancer agent are limited.…”

Biologically active isoquinoline alkaloids covering 2014–2018

“…98 The alkaloids caused cells to accumulate preferentially at G1 and G2 stages of the cell cycle with increased p16 expression and activity. [160][161][162][163] The potential targets also include mitochondrial function, DNA topoisomerase and arylamin Nacetyltransferase activity, Nuclear transcription factor-κB (NF-κB) signal pathway, the EGF and the VEGF receptors, and so forth. In human hepatoma cells, the alkaloid's antiproliferative effect might be mediated via the CAR metabolic and the arachidonic acid pathways, cPLA 2 , COX-2 gene expression and mitochondria-mediated apoptosis also were suppressed in vitro and in vivo, [164][165][166] Lycorine 321 Reports indicated that berberine mediates epigenetic reprogramming via HDAC inhibition and regulates Bcl-2/ Bax family proteins in the human lung cancer A549 cell line.…”

A Holistic View of Berberine Inhibiting Intestinal Carcinogenesis in Conventional Mice Based on Microbiome-Metabolomics Analysis

“…Multiple studies have confirmed that BBR had a variety of bioactivities, including anti-inflammatory (2,3), anti-microbial (4), and hypoglycemic and lipid-lowing efficacy (5,6). Several clinical and preclinical studies also demonstrate the ameliorative effect of berberine against several disorders including metabolic, neurological, cardiological, and gastrointestinal problems (7,8). Additionally, [9] conducted a double-blind, randomized, placebo-controlled clinical trial, and found that BBR at 0.3 g twice daily was safe and effective in reducing the risk of recurrence of colorectal adenoma (9).…”