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

dc.contributor.authorSantos, Felipe M.
dc.contributor.authorLatorre, Andreia O.
dc.contributor.authorHueza, Isis M. [UNIFESP]
dc.contributor.authorSanches, Daniel S.
dc.contributor.authorLippi, Luciana L.
dc.contributor.authorGardner, Dale R.
dc.contributor.authorSpinosa, Helenice S.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionPoisonous Plant Res Lab
dc.description.abstractSwainsonine 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.en
dc.description.affiliationUniv São Paulo, Dept Pathol, Fac Vet Med & Anim Sci, BR-05508270 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo UNIFESP, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, Brazil
dc.description.affiliationPoisonous Plant Res Lab, N Logan, UT 84341 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo UNIFESP, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.identifier.citationPhytomedicine. Jena: Elsevier Gmbh, Urban & Fischer Verlag, v. 18, n. 12, p. 1096-1101, 2011.
dc.publisherElsevier B.V.
dc.rightsAcesso restrito
dc.subjectCancer chemotherapyen
dc.subjectCis-diamminedichloroplatinum (II)en
dc.subjectGolgi alpha-mannosidase IIen
dc.subjectalpha-Mannosidase inhibitoren
dc.subjectAstragalus lentiginosusen
dc.subjectCell cycleen
dc.titleIncreased antitumor efficacy by the combined administration of swainsonine and cisplatin in vivoen