Alkaloids isolated from natural herbs as the anticancer agents

Abstract

Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made.

Figure 1

The chemical structures of berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine.

Figure 2

Berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine restrain cancer by modulating multiple signaling pathways, resulting in the inhibition of the initiation of carcinogenesis, induction of cell cycle arrest, apoptosis, autophagy, or differentiation, and inhibition of metastasis, angiogenesis, and so forth.

Figure 3

The schematic diagram of the molecular machinery and possible targets for the antineoplastic properties of berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine. ATF-2: activated transcription factor 2; Bax: Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; CDKs: cyclin-dependent kinases; COX-2: cyclooxygenase 2; CREB: cAMP response element-binding; DR-5: death receptor 5; ERK: extracellular signal-regulated kinase; FAK: focal adhesion kinase; Fas-L: Fas ligand; GADD153: growth arrest and DNA-damage-inducible gene 153; GSH: glutathione; GSK3β: glycogen synthase kinase 3β; HIF-1: hypoxia-inducible factor 1; MKP-1: mitogen-activated protein kinase phosphatase 1; MMP-2: matrix metalloproteinase 2; MMP-9: matrix metalloproteinase 9; NAT: N-acetyltransferase; NF-κB: nuclear factor κ-light-chain-enhancer of activated B cells; NOS: nitric oxide synthase; p38 MAPK: p38 mitogen-activated protein kinase; PKC: protein kinase C; P-gp: P-glycoprotein; ROS: reactive oxygen species; STAT-3: signal transducer and activator of transcription 3; TopI: topoisomerase I; TopII: topoisomerase II; u-PA: urokinase-type plasminogen-activator.