A Concise Total Synthesis of Deoxyschizandrin and Exploration of Its Antiproliferative Effects and those of Structurally Related Derivatives

Zheng, Shaojun; Aves, Sarah J.; Laraia, Luca; Galloway, Warren R. J. D.; Pike, Kurt G.; Wu, Wenjun; Spring, David R.

doi:10.1002/chem.201103530

Cited by 11 publications

(7 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intriguingly, a recent study has found that SchA has relatively little effects upon proliferation relative to its novel and nonnatural derivative that lacks the medium ring biaryl architecture. [ 27 ] Accordingly, we were stimulated to speculate that SchA exhibits an extensive scope of biological activities, which might be related to its structural characteristics. Definitely, the disparity of this sensitivity in different cells might contribute to the inconsistent consequences, which has been elaborated in a study of schizandrin.…”

Section: Discussionmentioning

confidence: 99%

MEG3 is restored by schisandrin A and represses tumor growth in choriocarcinoma cells

2020

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Schisandrin A (SchA) has been reported as a multidrug resistance-reversing agent; however, its antitumor effects have been rarely reported. Consequently, we attempted to explore whether SchA per se possesses an antitumor property in choriocarcinoma JEG-3 and BeWo cells and its potential mechanisms. JEG-3, BeWo, and HTR-8/SVneo cells were stimulated with SchA at different concentrations (10-100 μM), and cellular viability was evaluated with Cell Counting Kit-8. After stimulation with SchA, proliferation, apoptosis, migration, and invasion were detected by bromodeoxyuridine assay, Annexin V-fluorescein isothiocyanate/ propidium iodide (Annexin V-FITC/PI) method, and a Transwell system, in JEG-3 cells transfected with short hairpin-RNA for maternally expressed 3. Western blot was performed to quantify protein. MEG3 was examined by a quantitative reverse transcription-polymerase chain reaction. MEG3 was downregulated in choriocarcinoma tissues. SchA diminished cellular viability, decreased proliferative activity, inhibited migratory and invasive behaviors, and repressed phosphorylation of regulators of phosphatidylinositol 3 kinase/protein kinase B/nuclear factor κB (PI3K/AKT/NF-κB) signaling cascade in gestational choriocarcinoma cells. MEG3 was upregulated by SchA in JEG-3 and BeWo cells. SchA exhibited little suppressive effects in JEG-3 cells lacking MEG3. Besides, the phosphorylation of transducers was evoked in MEG3-silenced JEG-3 cells despite stimulation with SchA. SchA administration repressed the growth of JEG-3 and BeWo cells by upregulating MEG3. Besides, SchA blocked PI3K/AKT/NF-κB signal cascade by elevating MEG3. K E Y W O R D S choriocarcinoma, MEG3, PI3K/AKT/NF-κB, schisandrin A

show abstract

Section: Discussionmentioning

confidence: 99%

MEG3 is restored by schisandrin A and represses tumor growth in choriocarcinoma cells

2020

J Biochem & Molecular Tox

View full text Add to dashboard Cite

show abstract

“…Comparing with the published data and the UV spectra of standards, peaks 1–5 were identified as schisandrin, gomisin A, schisantherin B, deoxyschisandrin, and γ‐schisandrin, respectively.…”

Section: Resultsmentioning

confidence: 66%

An efficient strategy for the extraction and purification of lignans fromSchisandra chinensisby a combination of supercritical fluid extraction and high-speed counter-current chromatography

et al. 2013

View full text Add to dashboard Cite

An efficient strategy for extracting and separating five lignans from Schisandra chinensis (Turcz.) Baill has been developed using supercritical fluid extraction (SFE) and high-speed counter-current chromatography (HSCCC) in the present study. First, the extraction was performed by a preparative SFE system under 15 MPa of pressure at 36°C for 4 h. Then, the SFE extract was successfully separated and purified by HSCCC with a two-phase solvent system composed of n-hexane/ethyl acetate/methanol/water (6:4:5:5, 6:4:6:4, 6:4:8:2, v/v) in a stepwise elution mode. The fractions were analyzed by HPLC, and the chemical structures of the products were identified by ESI-MS and 1H NMR spectroscopy. As a result, a total of 12.5 mg of schisandrin at 98.0% purity, 7.1 mg of gomisin A at 98.1% purity, 1.8 mg of schisantherin B at 93.3% purity, 4.4 mg of deoxyschisandrin at 92.9% purity, and 6.8 mg of γ-schisandrin at 89.1% purity were obtained from 300 mg crude extract in a one-step purification.

show abstract

“…SchA belongs to the dibenzocyclooctadiene family of lignans (49). Its main feature is that the biaryl units are connected via aliphatic chains to form an eight-membered ring carbon skeleton (50).…”

Section: Resultsmentioning

confidence: 99%

Schizandrin A can inhibit non‑small cell lung cancer cell proliferation by inducing cell cycle arrest, apoptosis and autophagy

Zhu

Wang

et al. 2021

Int J Mol Med

View full text Add to dashboard Cite

Schizandrin A (SchA) can be extracted from the vine plant Schisandra chinensis and has been reported to confer various biologically active properties. However, its potential biological effects on non-small cell lung cancer (NSCLC) remain unknown. Therefore, the present study aims to address this issue. NSCLC and normal lung epithelial cell lines were first treated with SchA. Cell viability and proliferation were measured using CellTiter-Glo Assay and colony formation assays, respectively. PI staining was used to measure cell cycle distribution. Cell cycle-related proteins p53, p21, cyclin D1, CDK4, CDK6, cyclin E1, cyclin E2, CDK2 and DNA damage-related protein SOX4 were detected by western blot analysis. Annexin V-FITC/PI staining, DNA electrophoresis and Hoechst 33342/PI dual staining were used to detect apoptosis. JC-1 and DCFH-DA fluorescent dyes were used to measure the mitochondrial membrane potential and reactive oxygen species concentrations, respectively. Apoptosis-related proteins caspase-3, cleaved caspase-3, poly(ADP-ribose) polymerase (PARP), cleaved PARP, BimEL, BimL, BimS, Bcl2, Bax, caspase-9 and cleaved caspas-9 were measured by western blot analysis. Dansylcadaverine was used to detect the presence of the acidic lysosomal vesicles. The expression levels of the autophagy-related proteins LC3-I/II, p62/SQSTM and AMPKα activation were measured using western blot analysis. In addition, the autophagy inhibitor 3-methyladenine was used to inhibit autophagy. SchA treatment was found to reduce NSCLC cell viability whilst inhibiting cell proliferation. Low concentrations of SchA (10-20 µM) mainly induced G 1 /S-phase cell cycle arrest. By contrast, as the concentration of SchA used increases (20-50 µM), cells underwent apoptosis and G 2 /M-phase cell cycle arrest. As the treatment concentration of SchA increased from 0 to 50 µM, the expression of p53 and SOX4 protein also concomitantly increased, but the expression of p21 protein was increased by 10 µM SchA and decreased by higher concentrations (20-50 µM). In addition, the mRNA and protein expression levels of Bcl-like 11 (Bim) EL, BimL and BimS increased following SchA application. SchA induced the accumulation of acidic vesicles and induced a marked increase in the expression of LC3-II protein, suggsting that SchA activated the autophagy pathway. However, the expression of the p62 protein was found to be increased by SchA, suggesting that p62 was not degraded during the autophagic flux. The 3-methyladenine exerted no notable effects on SchA-induced apoptosis. Taken together, results from the present study suggest that SchA exerted inhibitory effects on NSCLC physiology by inducing cell cycle arrest and apoptosis. In addition, SchA partially induced autophagy, which did not result in any cytoprotective effects.

show abstract

A Concise Total Synthesis of Deoxyschizandrin and Exploration of Its Antiproliferative Effects and those of Structurally Related Derivatives

Cited by 11 publications

References 85 publications

MEG3 is restored by schisandrin A and represses tumor growth in choriocarcinoma cells

MEG3 is restored by schisandrin A and represses tumor growth in choriocarcinoma cells

An efficient strategy for the extraction and purification of lignans fromSchisandra chinensisby a combination of supercritical fluid extraction and high-speed counter-current chromatography

Schizandrin A can inhibit non‑small cell lung cancer cell proliferation by inducing cell cycle arrest, apoptosis and autophagy

Contact Info

Product

Resources

About