What is the anticancer mechanisms of berberine hydrochloride?

The potential antitumor activity of berberine hydrochloride has always been a subject of considerable interest because of its known ability to interact with nucleic acids. Its ability to bind specifically to oligonucleotides and to stabilize DNA triplexes or G-quadruplexes via telomerase and topoisomerase inhibition accounts for its antiproliferative activity.The predominant interaction between berberine hydrochloride and double-stranded or single-stranded DNA is electrostatic, and can be quantified in terms of the Hill model of cooperative interactions.Recent novel mechanisms have a higher propensity for autophagy and autophagic regulators. Wang et al found that berberine hydrochloride induced autophagic cell death which was diminished by 3-methyladenine, a cell death inhibitor, in the human hepatic carcinoma cell lines HepG2 and MHCC97-L, through activation of beclin-1 and inhibition of the mTOR signaling pathway.In addition, the autophagic marker, microtubule-associated protein-1 light chain 3 (LC3) was modified after administration of berberine hydrochloride in the human A549 lung cancer cell line, accompanied by shrinkage of tumor volume in a Lewis lung carcinoma model in mice, all of which indicates that autophagy might be important in cancer cell death.

In addition to autophagy and its interaction with nucleic acid, the hypoglycemic and hypolipidemic effects of berberine hydrochloride also point to a relationship between adipose tissue/adipocytes and tumorigenesis, through upregulation of mRNA and protein levels in adipose tissue, including peroxisome proliferator-activated receptor (PPAR) α, β, and γ, CDK9, and cyclin T1.3 Adipose tissue and adipocytes have a significant role in the tumor microenvironment,and SPARC (secreted protein acidic and rich in cysteine), an adiposity inhibitor, was suggested by Nagaraju and Sharma to be a potent anticancer molecule, and human adipose tissue-derived stem cells are known to be a source of carcinoma-associated fibroblasts in the presence of transforming growth factor β1. Further, adipose tissue-derived vascular endothelial growth factor and leptin promote adipogenesis in order to maintain the tumor microenvironment.Hirano et al have also suggested the existence of undefined factors derived from cancer cells which promote adipogenesis, further indicating a potential relationship between adipogenesis and development of cancer.In clinical lipofilling procedures undertaken for patients with breast cancer, there is an urgent need to clarify the issue of cancer recurrence and adipogenesis.The adipogenesis positive regulator, PPARγ, overexpressed in ERBB2-positive breast cancer cells, enables fatty acid synthesis, mainly to support energy demands and cell survival.Therefore, less toxic PPARγ agonists or antagonists, including berberine hydrochloride, are regarded as potential agents for improving adipose breast tissue and decreasing breast cancer risk, as well as suppressing proliferation and invasion of cancer cells.By inhibiting PPARγ protein expression and increasing PPARα mRNA levels, berberine hydrochloride has been shown to improve free fatty acid-induced insulin resistance in myotubes, and to suppress adipogenesis in white preadipocytes in humans and hepatic insulin resistance in diabetic hamsters.Berberine hydrochloride also prevented wasting of epididymal adipose tissue and ameliorated cancer cachexia in colon 26/clone 20-transplanted mice and colon 26/clone 20 cells,further highlighting the beneficial effect of this compound on adipose tissue in the tumor microenvironment.

Is there any supplyment for Berberine Hydrochloride?

Working as a potential natural compound in cancer therapy via its interaction with nucleic acid and regulation of cancer cells, as well as induction of autophagy, berberine hydrochloride augments the effects of chemotherapy/radiotherapy and has shown good prospects in cancer treatment.After the novel mechanisms by which it interferes with the development of adipose tissue and adipocyte metabolism in the tumor microenvironment were investigated, the efficacy and potential applications of berberine hydrochloride were highlighted and emphasized. Moreover, its extensive occurrence in various plant species and low toxicity suggest that berberine hydrochloride has the potential to become an effective antitumor agent in the future.

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