{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T03:14:19Z","timestamp":1770347659941,"version":"3.49.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,4,28]],"date-time":"2017-04-28T00:00:00Z","timestamp":1493337600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,4,28]],"date-time":"2017-04-28T00:00:00Z","timestamp":1493337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autophagy is a crucial and physiological process for cell survival from yeast to mammals, including protozoan parasites. <jats:italic>Toxoplasma gondii<\/jats:italic>, an intracellular parasite, typically exploits autophagic machinery of host cell; however host cell upregulates autophagy to combat the infection. Herein we tested the efficacy of Rottlerin, a natural polyphenol with autophagic promoting properties, against <jats:italic>Toxoplasma<\/jats:italic> infection on the chorioncarcinoma-derived cell line BeWo. We found that Rottlerin, at sub-toxic doses, induced morphological and biochemical alterations associated with autophagy and decreased <jats:italic>Toxoplasma<\/jats:italic> growth in infected cells. Although autophagy was synergically promoted by <jats:italic>Toxoplasma<\/jats:italic> infection in combination with Rottlerin treatment, the use of the autophagy inhibitor chloroquine revealed that Rottlerin anti-parasitic effect was largely autophagy-independent and likely mediated by the converging inhibitory effect of Rottlerin and <jats:italic>Toxoplasma<\/jats:italic> in host protein translation, mediated by mTOR inhibition and eIF2\u03b1 phosphorylation. Both events, which on one hand could explain the additive effect on autophagy induction, on the other hand led to inhibition of protein synthesis, thereby depriving <jats:italic>Toxoplasma<\/jats:italic> of metabolically essential components for multiplication. We suggest that modulation of the competition between pathogen requirement and host cell defense might be an attractive, novel therapeutic approach against <jats:italic>Toxoplasma<\/jats:italic> infection and encourage the development of Rottlerin-based new therapeutic formulations.<\/jats:p>","DOI":"10.1038\/s41598-017-01525-6","type":"journal-article","created":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T13:57:46Z","timestamp":1493042266000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Rottlerin-mediated inhibition of Toxoplasma gondii growth in BeWo trophoblast-like cells"],"prefix":"10.1038","volume":"7","author":[{"given":"Francesca","family":"Ietta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Maioli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Daveri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana","family":"Gonzaga Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafaela Jos\u00e9","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Romagnoli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Cresti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Maria Avanzati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luana","family":"Paulesu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bellisa de Freitas","family":"Barbosa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelica de Oliveira","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9010-7228","authenticated-orcid":false,"given":"Jos\u00e9","family":"Roberto Mineo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eloisa Am\u00e1lia Vieira","family":"Ferro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,4,28]]},"reference":[{"key":"1525_CR1","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1098\/rstb.2009.0237","volume":"365","author":"JA Kiel","year":"2010","unstructured":"Kiel, J. A. Autophagy in unicellular eukaryotes. Philos. Trans. R. Soc. Lond. B Biol. Sci. \n                           365, 819\u201330, doi:10.1098\/rstb.2009.0237 (2010).","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"1525_CR2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3858\/emm.2012.44.2.029","volume":"44","author":"JO Pyo","year":"2012","unstructured":"Pyo, J. O., Nah, J. & Jung, Y. K. Molecules and their functions in autophagy. Exp. Mol. Med. \n                           44, 73\u201380, doi:10.3858\/emm.2012.44.2.029 (2012).","journal-title":"Exp. Mol. Med."},{"key":"1525_CR3","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.gde.2009.12.004","volume":"20","author":"S Wilkinson","year":"2010","unstructured":"Wilkinson, S. & Ryan, K. M. Autophagy: an adaptable modifier of tumourigenesis. Curr. Opin. Genet. Dev. \n                           20, 57\u201364, doi:10.1016\/j.gde.2009.12.004 (2010).","journal-title":"Curr. Opin. Genet. 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Cancer Lett. \n                           360, 17\u201327, doi:10.1016\/j.canlet.2015.01.040 (2015).","journal-title":"Cancer Lett."},{"key":"1525_CR6","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/1756-3305-3-116","volume":"3","author":"CG Luder","year":"2010","unstructured":"Luder, C. G., Campos-Salinas, J., Gonzalez-Rey, E. & van Zandbergen, G. Impact of protozoan cell death on parasite-host interactions and pathogenesis. Parasit. Vectors \n                           3, 116, doi:10.1186\/1756-3305-3-116 (2010).","journal-title":"Parasit. Vectors"},{"key":"1525_CR7","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1586\/eri.12.58","volume":"10","author":"PA Moncada","year":"2012","unstructured":"Moncada, P. A. & Montoya, J. G. Toxoplasmosis in the fetus and newborn: an update on prevalence, diagnosis and treatment. Expert Rev. Anti Infect. Ther. \n                           10, 815\u201328, doi:10.1586\/eri.12.58 (2012).","journal-title":"Expert Rev. 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Autophagy activated by Toxoplasma gondii infection in turn facilitates Toxoplasma gondii proliferation. Parasitol. Res. \n                           113, 2053\u20138, doi:10.1007\/s00436-014-3853-5 (2014).","journal-title":"Parasitol. Res."},{"key":"1525_CR11","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1111\/j.1462-5822.2011.01745.x","volume":"14","author":"D Ghosh","year":"2012","unstructured":"Ghosh, D., Walton, J. L., Roepe, P. D. & Sinai, A. P. Autophagy is a cell death mechanism in Toxoplasma gondii. Cell. Microbiol. \n                           14, 589\u2013607, doi:10.1111\/j.1462-5822.2011.01745.x (2012).","journal-title":"Cell. Microbiol."},{"key":"1525_CR12","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1093\/emboj\/19.5.1087","volume":"19","author":"V Kumar","year":"2000","unstructured":"Kumar, V. et al. Functional interaction between RAFT1\/FRAP\/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of translation. 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Rottlerin inhibits ROS formation and prevents NFkappaB activation in MCF-7 and HT-29 cells. J. Biomed. Biotechnol. \n                           2009, 742936\u20137, doi:10.1155\/2009\/742936 (2009).","journal-title":"J. Biomed. Biotechnol."},{"key":"1525_CR16","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/S0304-4165(01)00203-3","volume":"1568","author":"R Ishii","year":"2001","unstructured":"Ishii, R., Horie, M., Saito, K., Arisawa, M. & Kitanaka, S. Inhibitory effects of phloroglucinol derivatives from Mallotus japonicus on nitric oxide production by a murine macrophage-like cell line, RAW 264.7, activated by lipopolysaccharide and interferon-gamma. Biochim. Biophys. Acta \n                           1568, 74\u201382, doi:10.1016\/S0304-4165(01)00203-3 (2001).","journal-title":"Biochim. Biophys. 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