Sanguinarine activates polycyclic aromatic hydrocarbon associated metabolic pathways in human oral keratinocytes and tissues

Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives

“…Furthermore, sanguinarine extract from bloodroot (Sanguinaria canadensis), previously used in oral hygiene products, was discontinued until a link between product administration and occurrence of leukoplakia was established [105,106] . Hepatic microsomes transform sanguinarine in a mutagenic epoxide and the same sanguinarine is capable of activating polycyclic aromatic hydrocarbon signaling [107] . However, related to this topic, the results available in literature are not univocal [3] .…”

Metabolism of sanguinarine in human and in rat: Characterization of oxidative metabolites produced by human CYP1A1 and CYP1A2 and rat liver microsomes using liquid chromatography–tandem mass spectrometry

“…Recently largest outbreak of ED appeared in the country involving over 2992 victims admitted to hospital and more than 67 deaths [1]. Although SA exhibits anti-bacterial and anti-inflammatory properties, in vitro studies using various human cells demonstrate that SA is a toxic compound exhibiting potential antitumor activity, as reported by Karp et al [2]. SA is shown to bind with rat tubulin to inhibit the microtubule polymerization and can readily intercalate double-stranded DNA, causing DNA single strand breaks.…”

“…Due to its structural similarity with polycyclic aromatic hydrocarbons, SA might act as a potential procarcinogen. Moreover, aryl hydrocarbon receptor metabolic signalling pathways might modulate SA activity, according to Karp et al [2]. Recently, in vitro metabolism studies in rat showed that cytochrome P4501A1 (CYP1A1) and P4501A2 (CYP1A2) were involved in SA metabolism.…”

“…Previous in vitro studies [2] indicated that CYP-dependent mono-oxygenations were involved in SA metabolism. These investigations conducted with rat or human liver microsomes suggested modulation by CYP1A.…”

Inhibitory effects of sanguinarine on human liver cytochrome P450 enzymes

“…For example, quinones (Sridhar et al, 2012) and noscapine (Fang et al, 2010) have been demonstrated as strong modulators of CYP enzymes. Indeed, SAG has been shown to induce the CYP1A gene expression via aryl hydrocarbon signal pathway (Karp et al, 2005), and inhibit human CYP1A1 and CYP1A2 (Vrba et al, 2004;Zdarilová et al, 2006), as well as rat CYP1A1, CYP1A2, CYP2D1, CYP2E1 and CYP3A1 (Reddy and Das, 2008;Eruvaram and Das, 2009).…”