Cytotoxic Sesquiterpenes from Sonchus oleraceus

Author(s):

Hongying Zhang, Yiding Wang, Shaojiu Wang, Qian Wang, Tianjing Wang, Jie Zhu* and Bing Liu   Pages 709 - 714 ( 6 )

Abstract:

<P>Background: Sonchus oleraceus is a large and widespread plant in the world. It is edible to humans as a leaf vegetable and is also used as a folklore medicinal herb in the treatment of infections and inflammatory disease, but limited research on its chemical constituents has been done. </P><P> Objective: To isolate and identify the bioactive ingredients from S. oleraceus. </P><P> 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. </P><P> Results: Two new sesquiterpenes were isolated from S. oleraceus and identified by NMR spectra and HR-ESIMS. 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 by the reduction in procaspase-3 expression, and the downregulation of Bcl-2 was associated with the enhancement of Bax expression. 1 could lead to the up-regulation of cytochrome c and activation of caspase-9. </P><P> Conclusion: 1 and 2 are new sesquiterpenes from S. oleraceus. 1 could induce apoptosis in A549 and H292 cells through Bax/caspase-9 pathway.<P>

Keywords:

Sonchus oleraceus, chemical constituent, sesquiterpene, cytotoxicity, apoptosis, Bax/caspase-9.

Affiliation:

Department of Emergency, The Fourth Affiliated Hospital of China Medical University, Shenyang, Department of Urology, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, Department of Emergency, The Fourth Affiliated Hospital of China Medical University, Shenyang, Department of Medical Oncology, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, Department of Emergency, The Fourth Affiliated Hospital of China Medical University, Shenyang, Department of Emergency, The Fourth Affiliated Hospital of China Medical University, Shenyang, College of Pharmacy, Harbin University of Commerce, Harbin

Graphical Abstract:

Read Full-Text article