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Mar Drugs
2014 Jul 24;128:4274-90. doi: 10.3390/md12084274.
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Cytotoxic and apoptosis-inducing activity of triterpene glycosides from Holothuria scabra and Cucumaria frondosa against HepG2 cells.
Wang J
,
Han H
,
Chen X
,
Yi Y
,
Sun H
.
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The cytotoxic effects of thirteen triterpene glycosides from Holothuria scabra Jaeger and Cucumaria frondosa Gunnerus (Holothuroidea) against four human cell lines were detected and their cytotoxicity-structure relationships were established. The apoptosis-inducing activity of a more potent glycoside echinoside A (1) in HepG2 cells was further investigated by determining its effect on the morphology, mitochondrial transmembrane potential (Δψm) and mRNA expression levels of the apoptosis-related genes. The results showed that the number of glycosyl residues in sugar chains and the side chain of aglycone could affect their cytotoxicity towards tumor cells and selective cytotoxicity. 1 significantly inhibited cell viability and induced apoptosis in HepG2 cells. 1 also markedly decreased the Δψm and Bcl-2/Bax mRNA express ratio, and up-regulated the mRNA expression levels of Caspase-3, Caspase-8 and Caspase-9 in HepG2 cells. Therefore, 1 induced apoptosis in HepG2 cells through both intrinsic and extrinsic pathway. These findings could potentially promote the usage of these glycosides as leading compounds for developing new antitumor drugs.
Figure 1. Chemical structures of triterpene glycosides 1–13 from H. scabra and C. frondosa. Glc: β-d-glucopyranosyl; MeGlc: 3-O-methyl-β-d-glucopyranosyl; Qui: β-d-quinovo-pyranosyl; Xyl: β-d-xylopyranosyl; S1: Qui-(1→2)-4-O-SO3Na-Xyl-; S2: MeGlc-(1→3)-Glc-(1→4)-Qui-(1→2)-4-O-SO3Na-Xyl-; S3: MeGlc-(1→3)-Xyl-(1→4)-Qui-(1→2)-4-O-SO3Na-Xyl-; S4: MeGlc-(1→3)-Xyl-(1→4)-[Xyl-(1→2)]-Qui-(1→2)-4-O-SO3Na-Xyl-; S5: MeGlc-(1→3)-Xyl-(1→4)-[Xyl-(1→2)]-Qui-(1→2)-4-O-SO3H-Xyl-; (a) and (b): Aglycone; (c–i): R2.
Figure 2. Effect of 1 on cell viability of HepG2 cells. HepG2 cells were treated with the various concentrations of 1 for 6 and 12 h, and cell viability was measured using the MTT assay. The values are presented as means ± SD (n = 5).
Figure 3. Morphological changes of HepG2 cells after treatment with 1 for 8 h. (a) Morphological changes visualized under a fluorescence microscope after acridine orange (OA) staining; (b) Morphological changes visualized under a fluorescence microscope after Hoechst 33342 staining. The figures shown are representative of three independent experiments.
Figure 4. Mitochondrial transmembrane potential changes of 1-treated HepG2 cells stained with JC-1 at the concentrations of 0 μg/mL (a); 2.5 μg/mL (b); 2.75 μg/mL (c) and 3.0 μg/mL (d). The figures shown are representative of three independent experiments.
Figure 5. Effect of 1 on the ratio of expression level between Bcl-2 and Bax mRNA in HepG2 cells. HepG2 cells were incubated with 1 at the various concentrations for the different time. The mRNA expression levels of β-actin, Bcl-2, and Bax were detected by RT-PCR using specific primers. The values are presented as means ± SD (n = 3). Significant differences with the untreated control group were designated as * p < 0.05, ** p < 0.01 and *** p < 0.001.
Figure 6. Effects of 1 on the mRNA expression level of Caspase-3, Caspase-8 and Caspase-9 in HepG2 cells. HepG2 cells were incubated with 1 at the various concentrations for the different time. The mRNA expression levels of β-actin, Caspase-3, Caspase-8 and Caspase-9 were detected by RT-PCR using specific primers. (a) The mRNA expression of Caspase-3 in HepG2 cells; (b) The mRNA expression of Caspase-8 and Caspase-9 in HepG2 cells. The values are presented as means ± SD (n = 3). Significant differences with the untreated control group were designated as * p < 0.05, ** p < 0.01 and *** p < 0.001.
Aminin,
Antitumor activity of the immunomodulatory lead Cumaside.
2010, Pubmed,
Echinobase
Aminin,
Antitumor activity of the immunomodulatory lead Cumaside.
2010,
Pubmed
,
Echinobase
Aminin,
Immunomodulatory action of monosulfated triterpene glycosides from the sea cucumber Cucumaria okhotensis: stimulation of activity of mouse peritoneal macrophages.
2010,
Pubmed
,
Echinobase
Antonov,
Triterpene glycosides from Antarctic sea cucumbers. 1. Structure of liouvillosides A1, A2, A3, B1, and B2 from the sea cucumber Staurocucumis liouvillei: new procedure for separation of highly polar glycoside fractions and taxonomic revision.
2008,
Pubmed
,
Echinobase
Avilov,
Synaptosides A and A1, triterpene glycosides from the sea cucumber Synapta maculata containing 3-O-methylglucuronic acid and their cytotoxic activity against tumor cells.
2008,
Pubmed
,
Echinobase
Chludil,
Cytotoxic and antifungal triterpene glycosides from the Patagonian sea cucumber Hemoiedema spectabilis.
2002,
Pubmed
,
Echinobase
Dang,
Two new triterpene glycosides from the Vietnamese sea cucumber Holothuria scabra.
2007,
Pubmed
,
Echinobase
Delhalle,
An introduction to the molecular mechanisms of apoptosis.
2003,
Pubmed
Elmore,
Apoptosis: a review of programmed cell death.
2007,
Pubmed
Haefner,
Drugs from the deep: marine natural products as drug candidates.
2003,
Pubmed
Han,
Two new cytotoxic triterpene glycosides from the sea cucumber Holothuria scabra.
2009,
Pubmed
,
Echinobase
Jin,
Differential effects of triterpene glycosides, frondoside A and cucumarioside A2-2 isolated from sea cucumbers on caspase activation and apoptosis of human leukemia cells.
2009,
Pubmed
,
Echinobase
Kalinin,
System-theoretical (Holistic) approach to the modelling of structural-functional relationships of biomolecules and their evolution: an example of triterpene glycosides from sea cucumbers (Echinodermata, holothurioidea).
2000,
Pubmed
,
Echinobase
Kalinin,
Hemolytic activities of triterpene glycosides from the holothurian order Dendrochirotida: some trends in the evolution of this group of toxins.
1996,
Pubmed
,
Echinobase
Kim,
Triterpene glycosides from sea cucumbers and their biological activities.
2012,
Pubmed
,
Echinobase
Li,
Echinoside A, a new marine-derived anticancer saponin, targets topoisomerase2alpha by unique interference with its DNA binding and catalytic cycle.
2010,
Pubmed
,
Echinobase
Li,
Review of the apoptosis pathways in pancreatic cancer and the anti-apoptotic effects of the novel sea cucumber compound, Frondoside A.
2008,
Pubmed
,
Echinobase
Maier,
Two new cytotoxic and virucidal trisulfated triterpene glycosides from the Antarctic sea cucumber Staurocucumis liouvillei.
2001,
Pubmed
,
Echinobase
Newman,
Marine natural products and related compounds in clinical and advanced preclinical trials.
2004,
Pubmed
Perez,
Impact, mechanisms, and novel chemotherapy strategies for overcoming resistance to anthracyclines and taxanes in metastatic breast cancer.
2009,
Pubmed
San-Miguel,
N-acetyl-cysteine protects liver from apoptotic death in an animal model of fulminant hepatic failure.
2006,
Pubmed
Silchenko,
Constituents of the sea cucumber Cucumaria okhotensis. Structures of okhotosides B1-B3 and cytotoxic activities of some glycosides from this species.
2008,
Pubmed
,
Echinobase
Stonik,
Toxins from sea cucumbers (holothuroids): chemical structures, properties, taxonomic distribution, biosynthesis and evolution.
1999,
Pubmed
,
Echinobase
Sun,
Induction of apoptosis in HeLa cells by 3beta-hydroxy-12-oleanen-27-oic acid from the rhizomes of Astilbe chinensis.
2006,
Pubmed
Villa,
Marine natural product drug discovery: Leads for treatment of inflammation, cancer, infections, and neurological disorders.
2010,
Pubmed
Wang,
The Inhibitory Effect of 3 β -Hydroxy-12-oleanen-27-oic Acid on Growth and Motility of Human Hepatoma HepG2 Cells through JNK and Akt Signaling Pathway.
2013,
Pubmed
Zhang,
Astilbotriterpenic acid induces growth arrest and apoptosis in HeLa cells through mitochondria-related pathways and reactive oxygen species (ROS) production.
2009,
Pubmed
Zhang,
Cytotoxic triterpene glycosides from the sea cucumber Pseudocolochirus violaceus.
2007,
Pubmed
,
Echinobase
Zhao,
In vitro and in vivo anti-tumour activities of echinoside A and ds-echinoside A from Pearsonothuria graeffei.
2012,
Pubmed
,
Echinobase
Zhao,
Differential effects of sulfated triterpene glycosides, holothurin A1, and 24-dehydroechinoside A, on antimetastasic activity via regulation of the MMP-9 signal pathway.
2010,
Pubmed
,
Echinobase
Zhong,
Compositional characteristics and antioxidant properties of fresh and processed sea cucumber (Cucumaria frondosa).
2007,
Pubmed
,
Echinobase
Ziedan,
The development of pro-apoptotic cancer therapeutics.
2008,
Pubmed
Zou,
Intercedensides A-C, three new cytotoxic triterpene glycosides from the sea cucumber Mensamaria intercedens Lampert.
2003,
Pubmed
,
Echinobase
Zou,
Intercedensides D-I, cytotoxic triterpene glycosides from the sea cucumber Mensamaria intercedens Lampert.
2005,
Pubmed
,
Echinobase
