Increased antitumor efficacy by the combined administration of swainsonine and cisplatin in vivo

Increased antitumor efficacy by the combined administration of swainsonine and cisplatin in vivo

Author Santos, Felipe M. Google Scholar
Latorre, Andreia O. Google Scholar
Hueza, Isis M. Autor UNIFESP Google Scholar
Sanches, Daniel S. Google Scholar
Lippi, Luciana L. Google Scholar
Gardner, Dale R. Google Scholar
Spinosa, Helenice S. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Poisonous Plant Res Lab
Abstract Swainsonine is a natural alpha-mannosidase inhibitor found in numerous poisonous plants, such as Astragalus lentiginosus. Its mechanism of action is through the inhibition of Golgi alpha-mannosidase II activity in the N-glycan biosynthesis pathway. As a result, swainsonine inhibits the production of complex beta 1,6-branched N-linked glycans, which are related to the malignant phenotype of tumor cells. in this study, we investigated whether treatment with swainsonine affects the sensitivity of Ehrlich ascites carcinoma (EAC) cells to cisplatin. To this end, male C57BL/6 mice were treated with swainsonine (SW - 0.5 mg/kg, i.p., twice-daily for ten days) and/or cisplatin (Cis - 0.25 mg/kg, i.p., every other day for a total of five applications) two days after transplantation with EAC cells. the results showed a greater reduction in the ascites volume in mice from the CisSW group (63.5%) than in mice from the Cis group (45.7%), an elevated induction of apoptosis by CisSW treatment when compared to Cis alone, as demonstrated by higher percentage of cells in the subG1 phase in that group (p < 0.0001 Kruskal-Wallis, p < 0.0001 control vs. CisSW, p < 0.001 Co vs. Cis post-test Dunn), and an increase in the median survival from 12.5 days observed in the control group to 27 days in the CisSW group, which corresponds to a 116% survival increase (p = 0.0022 Co vs. CisSW Log-rank test). in addition, the mice from the Cis group had a median survival of only 15 days, an increase of just 20% compared to controls. Our results indicate that swainsonine increases the sensitivity of EAC cells to cisplatin. (C) 2011 Elsevier GmbH. All rights reserved.
Keywords Cancer chemotherapy
Cis-diamminedichloroplatinum (II)
Golgi alpha-mannosidase II
alpha-Mannosidase inhibitor
Astragalus lentiginosus
Cell cycle
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2011-09-15
Published in Phytomedicine. Jena: Elsevier Gmbh, Urban & Fischer Verlag, v. 18, n. 12, p. 1096-1101, 2011.
ISSN 0944-7113 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1096-1101
Access rights Closed access
Type Article
Web of Science ID WOS:000296304600012

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