Recent Advances in Berberine Inspired Anticancer Approaches: From Drug Combination to Novel Formulation Technology and Derivatization

Abstract

Berberine is multifunctional natural product with potential to treat diverse pathological conditions. Its broad-spectrum anticancer effect through direct effect on cancer cell growth and metastasis have been established both in vitro and in vivo. The cellular targets that account to the anticancer effect of berberine are incredibly large and range from kinases (protein kinase B (Akt), mitogen activated protein kinases (MAPKs), cell cycle checkpoint kinases, etc.) and transcription factors to genes and protein regulators of cell survival, motility and death. The direct effect of berberine in cancer cells is however relatively weak and occur at moderate concentration range (10–100 µM) in most cancer cells. The poor pharmacokinetics profile resulting from poor absorption, efflux by permeability-glycoprotein (P-gc) and extensive metabolism in intestinal and hepatic cells are other dimensions of berberine’s limitation as anticancer agent. This communication addresses the research efforts during the last two decades that were devoted to enhancing the anticancer potential of berberine. Strategies highlighted include using berberine in combination with other chemotherapeutic agents either to reduce toxic side effects or enhance their anticancer effects; the various novel formulation approaches which by order of magnitude improved the pharmacokinetics of berberine; and semisynthetic approaches that enhanced potency by up to 100-fold.

The Quest to Enhance the Efficacy of Berberine for Type-2 Diabetes and Associated Diseases: Physicochemical Modification Approaches

“…With the aim of promoting research in this field, our recent communication scrutinised the gut microbiota as a hidden therapeutic target that dictate the diverse pharmacology of berberine [27]. By using berberine as an inspiring lead natural product, recent attempts to enhance its anticancer therapeutic efficacy through semisynthetic approaches have also been reported [28]. In continuation of this effort, recent advances in the physicochemical modifications of berberine to target T2D and associated diseases is scrutinised herein.…”

Prosopis juliflora leave extracts induce cell death of MCF-7, HepG2, and LS-174T cancer cell lines

“…When DNA is damaged, cell cycle checkpoints indicate the proper execution of the cycle events in different pathways, as; a) blocking the cell entry into mitosis that is denoted by G2/M phase arrest (Taylor and Stark, 2001[ 34 ]), b) preventing DNA duplication as referred by S-phase arrest (Taylor and Stark, 2001[ 34 ]). However, the cell cycle arrest and apoptotic pathways depend on the cell type and the anticancer agent (Habtemariam, 2020[ 13 ]). Therefore, the ability of the different cancer cell lines; MCF-7, HePG2 and LS-174T, to release the mitochondrial or nucleic intrinsic factors in response to the tested plant extracts' compounds was variable in sensitivity.…”

A review on herbal drug loaded into pharmaceutical carrier techniques and its evaluation process

“…Several drugs that also possess natural therapeutic agents in their composition are already available commercially; their applications and names are as follows [46]: malaria treatment (Artemotil derived from Artemisia annua, a traditional Chinese medicine plant) and cancer treatment (paclitaxel and its analogs derived from the Taxus brevifolia plant; vinblastine and vincristine extracted from Catharanthus roseus; liver disease (silymarin from Silybum marianum)).…”