Antiproliferative and cytotoxic activities of furocoumarins of Ducrosia anethifolia

Abstract

Context: Phytochemical and pharmacological data on Ducrosia anethifolia (DC.) Boiss. (Apiaceae), an Iranian medicinal plant, are scarce; however, furocoumarins are characteristic compounds of D. anethifolia.Objective: Our experiments identify the secondary metabolites of D. anethifolia and assess their antitumor and anti-multidrug resistance activities.Materials and methods: Pure compounds were isolated from the extract of aerial parts of the plant by chromatographic methods. Bioactivities were tested on multidrug resistant and sensitive mouse T-lymphoma cell lines. The inhibition of the cancer MDR efflux pump ABCB1 was evaluated by flow cytometry (at 2 and 20 µM). A checkerboard microplate method was applied to study the interactions of furocoumarins and doxorubicin. Toxicity was studied using normal murine NIH/3T3 fibroblasts.Results: Thirteen pure compounds were isolated, nine furocoumarins namely, pabulenol (1), (+)-oxypeucedanin hydrate (2), oxypeucedanin (3), oxypeucedanin methanolate (4), (−)-oxypeucedanin hydrate (5), imperatorin (6), isogospherol (7), heraclenin (8), heraclenol (9), along with vanillic aldehyde (10), harmine (11), 3-hydroxy-α-ionone (12) and 2-C-methyl-erythrytol (13). Oxypeucedanin showed the highest in vitro antiproliferative and cytotoxic activity against parent (IC50 = 25.98 ± 1.27, 40.33 ± 0.63 µM) and multidrug resistant cells (IC50 = 28.89 ± 0.73, 66.68 ± 0.00 µM), respectively, and exhibited slight toxicity on normal murine fibroblasts (IC50 = 57.18 ± 3.91 µM).Discussion and conclusions: Compounds 2, 3, 5, 7, 10–13 were identified for the first time from the Ducrosia genus. Here, we report a comprehensive in vitro assessment of the antitumor activities of D. anethifolia furocoumarins. Oxypeucedanin is a promising compound for further investigations for its anticancer effects.

Anticancer Potential of Furanocoumarins: Mechanistic and Therapeutic Aspects

“…Thus, as to improve genuine treatments for various sorts of tumors, nanomedicine has developed new strategies coordinated to build the efficacy of medications focusing on tumors and limit their side effects [136,137]. Furanocoumarin-loaded lipid-polymer-hybrid-nanoparticles represent an additional option for sustained release of these molecules to improve efficacy and synergistic effects with other anticancer agents and against MDR cancers [108,138,139]. To date, most focus has been on in vitro studies, making it hard to reach solid conclusions on the efficacy of furanocoumarins in vivo.…”

Deverra tortuosa (Desf.) DC from Saudi Arabia as a new source of marmin and furanocoumarins derivatives with α-glucosidase, antibacterial and cytotoxic activities

“…In addition, the cytotoxic activity of the 2 monoterpenoid coumarins (1 and 2) and the furocoumarins (compounds 3) was reported for the first time. Compared with previous studies, the 4 compounds showed relatively low cytotoxic activity (Thanh et al, 2004;Sancho et al, 2004;Chauthe et al, 2015;Mottaghipisheh et al, 2018). Coumarin derivatives were described to possess several therapeutic applications such as antitumor therapy (Musa et al, 2008), in vivo and in vitro cytotoxic activity (Detsi et al, 2017;Oueslati et al, 2019).…”

Review of Natural Compounds for the Management and Prevention of Lymphoma

“…These results indicated that FXOH induced apoptosis by decreasing NFκB-DNA binding activity, followed by inhibition of antiapoptotic and cell cycle regulatory proteins. Mottaghipisheh et al confirmed that various compounds isolated from Ducrosia anethifolia inhibited proliferation in L5178Y parent (PAR) and multidrug resistance (MDR) cells [37]. Among compounds, pabulenol, (þ)-oxypeucedanin hydrate, oxypeucedanin, oxipeudanin methanolated, imperatorin, isogospherol, heraclenin, and heraclenol had IC50 values for antiproliferation against L5178Y MDR cells, as well as L5178Y PAR cells.…”