Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives

Abstract

Historically, natural products have represented a significant source of anticancer agents, with plant-derived drugs becoming increasingly explored. In particular, sanguinarine is a benzophenanthridine alkaloid obtained from the root of Sanguinaria canadensis , and from other poppy Fumaria species, with recognized anti-microbial, anti-oxidant and anti-inflammatory properties. Recently, increasing evidence that sanguinarine exibits anticancer potential through its capability of inducing apoptosis and/or antiproliferative effects on tumor cells, has been proved. Moreover, its antitumor seems to be due not only to its pro-apoptotic and inhibitory effects on tumor growth, but also to its antiangiogenic and anti-invasive properties. Although the precise mechanisms underlying the antitumor activity of this compound remain not fully understood, in this review we will focus on the most recent findings about the cellular and molecular pathways affected by sanguinarine, together with the rationale of its potential application in clinic. The complex of data currently available suggest the potential application of sanguinarine as an adjuvant in the therapy of cancer, but further pre-clinical studies are needed before such an antitumor strategy can be effectively translated in the clinical practice.

Enhancement of Macarpine Production in Eschscholzia Californica Suspension Cultures under Salicylic Acid Elicitation and Precursor Supplementation

“…However, if the production of sanguinarine is inducible by various exogenous elicitors that mimic the pathogen attack (biotic elicitation), the production of macarpine in intact plants or cell cultures of natural producers is also increased. Recent studies have revealed the prospective biological activities of macarpine toward cancer cells [12,14,24], but extensive testing is limited by its availability from natural sources.…”

“…In general, quaternary benzophenanthridine alkaloids possess a broad spectrum of biological activities, including anti-bacterial, anti-viral, anti-oxidative, anti-inflammatory and neuroprotective properties [9][10][11]. Recently, the strong antiproliferative and apoptotic effects of sanguinarine, chelerythrine, macarpine and chelirubine against a broad spectrum of human cancer cell lines have been identified, which predetermine their use as an adjuvants in cancer therapy [12][13][14]. Besides the mentioned activities, macarpine evinces an ability to interact with DNA and its fluorescence properties could be used as a DNA probe for fluorescence microscopy and flow cytometry including analyses of the cell cycle [1].…”

The natural compound sanguinarine perturbs the regenerative capabilities of planarians

“…On the other hand, other studies report concerns of toxicity linked to increased risks of oral leukoplakia, questioning safety of the use of this compound in dental care products (Maskarenhas et al, 2002). Sanguinarine also appears to exert interesting anticancer activities, playing a crucial role in various steps of tumor cell development and metastases (Gaziano et al, 2016). Furthermore, this compound has been incorporated into food additives to promote animal growth, exhibiting properties that are of veterinary relevance (Kosina et al, 2004).…”

“…Although a number of literature data underlines the promising therapeutic importance of sanguinarine (Gaziano et al, 2016), there is only limited information about the effects of this alkaloid during embryonic development (Chan, 2014). Application of these results to clinical practice requires further in vivo studies to define its possible effects on developing organisms.…”

Sanguinarine Induces Apoptosis of Human Oral Squamous Cell Carcinoma KB Cells via Inactivation of the PI3K/Akt Signaling Pathway

“…Recent studies on sanguinarine have documented a wide spectrum of therapeutic properties, including anti-microbial [Miao et al, 2011;Yang et al, 2012], anti-inflammatory [Niu et al, 2012;Li et al, 2014], antioxidative [Firatli et al, 1994;Vrba et al, 2004], immunomodulatory [Senchina et al, 2009;Vlachojannis et al, 2012] and anti-angiogenic [Eun and Koh, 2004;Basini et al, 2007] effects. Sanguinarine has also demonstrated anti-cancer activities, due to its ability to inhibit cell growth or to induce cell cycle arrest and apoptotic pathways in distinct cancer cell types [Gupta et al, 2010;Gaziano et al, 2016]. Interestingly, this agent does not show any apoptotic effects on normal cells, making it highly promising as an anticancer drug [Ahmad et al, 2000].…”