In Vivo anti-tumor effect of Eckol, a phlorotannin component isolated from brown algae, associated with regulating dendritic cells in sarcoma 180 (S180) xenografts-bearing mice

[Speaker] Jun Wang:1
[Co-author] Mengya Zhang:1, Shuqi Zhao:1, Juan Liu:1, Xianmin Hu:1
1:Department of Pharmacology, Medical College, Wuhan University of Science and Technology, China

Background: Eckol is a marine natural product with potent biological activities, such as the antioxidant, cytoprotective properties, neuroprotective effect and anti-adipogenic activity. Previous study showed treatment of Eckol on U373 glioma cells cultured in sphere forming condition, which was induced by epidermal growth factor and basic fibroblast growth factor, dramatically suppressed the cell proliferation and the formation of spheres. In this study, we investigated the in vivo antitumor effect and possible mechanisms of Eckol on xenografted sarcoma 180 (S180) in mice.
Methods: Male Kunming mice were randomly divided into 4 groups of 15 animals in each group: (1-3) Eckol treatment groups: orally administered with Eckol at low (0.25mg
/kg), middle(0.5mg/kg) and high (1.0mg/kg),respectively; (4) model control group: orally administered with the same volume of distilled water. After Eckol pretreatment for 1 week, S180 cells were implanted subcutaneously into the left hind groin of all the animals. On day 14 after inoculation, all mice were sacrificed to examine cytokine levels in serum, spleen T lymphocyte proliferation and dendritic cell (DC) surface molecules. The sarcoma tissues were isolated and weighted for histopathological examination, TUNEL analysis and Western blotting analysis. In addition, the in vitro direct effect of Eckol on S180 cells were measured using MTT assay.
Results: Eckol significantly inhibited the growth of S180 sarcoma at the dose of 0.5 or 1.0 mg/kg. Histopathological examination revealed tumor necrosis and TUNEL analysis showed that cell apoptosis was increased in the Eckol-treated group. Western blotting analysis also revealed the increased expression of cleaved caspase-3 and decreased expression of bcl-2 by Eckol. However, treatment of S180 cells with Eckol at 5-20ug/ml did not result in a significant change in cell viability as assessed by MTT assay. But in vivo treatment of Eckol enhanced spleen T lymphocyte proliferation, induced Th1-biased cytokine response. And Eckol-treated bone marrow derived DCs were characterized as high expression of MHC class2 and CD86 molecules.
Conclusions: The in vivo antitumor effect of Eckol in S180 xenografts bearing mice is associated with stimulating DCs and then upregulating the immune response.
Acknowledgements: This work was supported by the National Nature Science Foundation of China(81602108).
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