Cytotoxic Sesquiterpenes from Sonchus oleraceus

(E-pub Abstract Ahead of Print)

Author(s): Hongying Zhang, Yiding Wang, Shaojiu Wang, Qian Wang, Tianjing Wang, Jie Zhu*, Bing Liu.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

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Abstract:

Background: Sonchus oleraceus is a large and widespread plant in the world. It is edible to humans as a leaf vegetable and also a folklore medicinal herb in the treatment of infections and inflammatory disease, but limited research on the chemical constituents of was presented.

Objective: To isolate and identified the bioactive ingredients from S. oleraceus.

Methods: 20kg of S. oleraceus was extracted twice with 75% alcohol. The concentrated extract was suspended in H2O and partitioned with petroleum ether, dichloromethane, ethyl acetate and n-butanol, respectively. The ethyl acetate phase was subjected to repeated normal chromatography on a silica gel column chromatography and eluted with a gradient of CH2Cl2-MeOH to give 12 crude fractions. Fraction 6 was subjected to ODS silica gel column chromatography, Sephadex LH-20 and HPLC to yield 1 and 2. Cell viability of 1 and 2 on A549, H292 and Caco2 cell lines were assayed by MTT method. Apoptosis analysis and apoptosis related proteins were detected subsequently.

Results: Two new sesquiterpenes were isolated from S. oleraceus and identified by NMR spectra and HR-ESI-MS. 1 selectively suppressed the viability of A549 and H292 cells with IC50 values of 14.2, and 19.5μM respectively, while possessing no cytotoxicity against Caco2 cells (IC50 > 100μM). 2 did not exhibit cytotoxicity against A549, H292 and Caco2 cells (IC50 > 100μM). 1 significantly decreased the density of live cells and could cause cell apoptosis at 10 and 20μM in a dose-dependent manner. After treatment of 1 for 24h, the level of cleaved caspase-3 was increased accompanied with the reduction in procaspase-3 expression, and the down-regulation of Bcl-2 was associated with the enhancement of Bax expression. 1 could led to the up-regulation of cytochrome c and activation of caspase-9.

Conclusion: 1 and 2 are new sesquiterpenes from S. oleraceus. 1 could induce apoptosis in A549 and H292 cells through Bax/caspase-9 pathway.

Keywords: Sonchus Oleraceus, Chemical Constituent, Sesquiterpene, Cytotoxicity, Apoptosis, Bax/Caspase-9

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Article Details

(E-pub Abstract Ahead of Print)
DOI: 10.2174/1871520620666200101152934
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