Cytotoxic and anti-migration effects of cardiac glycosides from Gomphocarpus fruticosus and Kanahia laniflora on hepatocellular carcinoma; LC-MS/MS profiling, in vitro bioassay and molecular docking study
Helmi A. Mokbel , Seham S. El Hawary , Rasha M. Allam , Ahmed H. Eldesoky , Ali M. El-Halawany , Amira K. El-Motayam
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引用次数: 0
Abstract
Hepatocellular carcinoma (HCC) is one of the most aggressive tumors, having a high incidence and mortality rate globally. This study investigated the anticancer effects of Gomphocarpus fruticosus (L.) Ait and Kanahia laniflora (Forsk.) Schum. against HCC using HepG2 cells in vitro. Apoptosis and cell cycle analysis were assessed by flow cytometry to investigate the possible mechanism of action. In addition, antimigratory activity was evaluated by scratch/wound healing assay. G. fruticosus and K. laniflora. significantly (P < 0.05) suppressed the growth of HepG2, with IC50 values of 0.07 µg/ml and 0.77 µg/ml, respectively. In addition, both plants induced S- and G2/M phases arrest while promoting apoptosis. Besides, they markedly reduced the migration of HepG2 cells. LC-MS/MS study revealed the tentative identification of sixty-six and twenty-three chemical compounds in G. fruticosus and K. laniflora, respectively, including diverse classes of phytochemicals. Ten of these compounds were found in both species. A docking study was carried out to investigate the binding potency and mechanism of cardenolides in both plants to Na+, K+-ATPase pump as a target for apoptosis in cancer cells. Generally, compared to common cardenolides, the dioxane doubly linked cardenolide glycosides have more potent inhibition on Na+,K+-ATPase. Finally, the compounds, hydroxyfrugoside (20), 3′-Epi-19-oxo-5,6-didehydrogomphoside-3′O-glucopyranoside (23), hydroxycalotropin (25), frugoside (30) and 3,14-Dihydroxycard-20(22)-ene-3-O-[(6-O-feruloyl)-glucopyranoside] (33) revealed the most potent binding affinity to this target. This study proposed the use of G. fruticosus and K. laniflora for the isolation and development of anticancer medications.
期刊介绍:
The South African Journal of Botany publishes original papers that deal with the classification, biodiversity, morphology, physiology, molecular biology, ecology, biotechnology, ethnobotany and other botanically related aspects of species that are of importance to southern Africa. Manuscripts dealing with significant new findings on other species of the world and general botanical principles will also be considered and are encouraged.