Identification and Quantification of the Main Active Anticancer Alkaloids from the Root of Glaucium flavum

Abstract

Glaucium flavum is used in Algerian folk medicine to remove warts (benign tumors). Its local appellations are Cheqiq el-asfar and Qarn el-djedyane. We have recently reported the anti-tumoral activity of Glaucium flavum root alkaloid extract against human cancer cells, in vitro and in vivo. The principal identified alkaloid in the extract was protopine. This study aims to determine which component(s) of Glaucium flavum root extract might possess potent antitumor activity on human cancer cells. Quantitative estimation of Glaucium flavum alkaloids was realized by HPLC-DAD. Glaucium flavum effect on human normal and cancer cell viability was determined using WST-1 assay. Quantification of alkaloids in Glaucium flavum revealed that the dried root part contained 0.84% of protopine and 0.07% of bocconoline (w/w), while the dried aerial part contained only 0.08% of protopine, glaucine as the main alkaloid, and no bocconoline. In vitro evaluation of the growth inhibitory activity on breast cancer and normal cells demonstrated that purified protopine did not reproduce the full cytotoxic activity of the alkaloid root extract on cancer cell lines. On the other hand, bocconoline inhibited strongly the viability of cancer cells with an IC50 of 7.8 μM and only a low cytotoxic effect was observed against normal human cells. Our results showed for the first time that protopine is the major root alkaloid of Glaucium flavum. Finally, we are the first to demonstrate a specific anticancer effect of Glaucium flavum root extract against breast cancer cells, which can be attributed, at least in part, to bocconoline.

Halophytic herbs of the Mediterranean basin: An alternative approach to health

“…Moreover, Arafa et al (2016) reported that ethanol extracts from the aerial parts of the plant possessed analgesic, antibacterial, anti-inflammatory, antifungal and cytotoxic activities. Similarly, Hadjiakhoondi et al (2013) observed that the aerial parts alkaloid extracts exhibited cytotoxic effects against colon adenocarcinoma cell lines (HT-29, Caco-2), while Bournine et al (2013) reported that the root methanolic extracts displayed anticancer effects against breast cancer cells. Other health effects include depressive effects of various plant parts extracts on the central nervous system (CNS) and blood glucose levels (Cabo et al, 1988(Cabo et al, , 1987, while the main bioactive compound of the species (glaucine) has been associated with various pharmacological properties, such as antitussive, antiparkinsonic, hypotensive, antiviral, cardiovascular and cytotoxic effects (Orallo et al, 1995;Spasova et al, 2008).…”

“…1c). Moreover, Bournine et al (2013) studied the chemical composition of roots and isolated two new alkaloids, namely protopine and bocconoline. Two more alkaloids were also isolated and identified in aerial parts as N,N-dimethyl-hernovine and sanguinarine (Och et al, 2017).…”

Isolation and Characterization of O-methyltransferases Involved in the Biosynthesis of Glaucine in Glaucium flavum

“…Previously detected BIAs generally belong to the protopine, benzophenanthridine, or aporphine subgroups. HPLC-UV analysis showed that glaucine predominates in aerial organs, whereas protopine occurs mostly in roots (Bournine et al, 2013). Isocorydine, an aporphine alkaloid with one free hydroxyl group, has also been reported in G. flavum (Daskalova et al, 1988;Peled et al, 1988;Kintsurashvili and Vachnadze 2000;Petitto et al, 2010;).…”

Antiproliferative activity ofHumulus lupulusextracts on human hepatoma (Hep3B), colon (HT-29) cancer cells and proteases, tyrosinase,β-lactamase enzyme inhibition studies

“…As a result, we suggest that H. lupulus extracts at high concentration might have an effect on the viability of human colon cancer cells with a similar anti-apoptotic and/or an antioxidant mechanisms. To explain certain mechanism(s) of this potential dual role of H. lupulus on survival and growth of the cancer cells, and to precise cut off value and concentration limits of H. lupulus extracts before its use as an anti-neoplastic agent will need some further studies 26 .…”