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Isothiocyanates (ITCs) induce autophagy in cancer cells, however, their impact on primary cells remains insufficiently explored, particularly in non-epithelial cells. The aim of this study was to investigate whether ITCs induce autophagy in primary (non-immortalized) mesenchymal cells and if so, to determine the molecular mechanism underlying its activation and consequences on cell functioning.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Primary human dermal fibroblasts (HDFa) and prostate cancer cells (PC3) as well as two ITCs, sulforaphane and phenethyl isothiocyanate, were applied. Cell viability was measured by the MTT test, protein synthesis - by <jats:sup>3<\/jats:sup>H-leucine incorporation, and protein level - by immunoblotting. A number of mutant huntingtin (mHtt) aggregates was assessed by fluorescence microscopy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Both ITCs efficiently induced autophagy in fibroblasts which coincided with suppression of mTORC1 \u2013 a negative autophagy regulator - and protein synthesis arrest. A dephosphorylation of mTORC1 substrate, S6K1, and ribosomal S6 protein was preceded by activation of AMPK, an inhibitor of mTORC1 and autophagy activator. A similar response was observed in phenethyl isothiocyanate-treated prostate cancer cells. We also showed that ITCs-induced autophagy and\/or translation block do not affect cells viability and can protect cells against an accumulation of mHtt aggregates \u2013 a main cause of Huntington\u2019s disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our study showed that ITCs induce autophagy and inhibit protein synthesis in both primary mesenchymal and cancer cells <jats:italic>via<\/jats:italic> modulation of the AMPK-mTORC1-S6K1 pathway. Moreover, it suggests that ITCs might have a potential in developing therapeutics for Huntington\u2019s disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00394-024-03539-z","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T14:05:04Z","timestamp":1734357904000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Isothiocyanates induce autophagy and inhibit protein synthesis in primary cells via modulation of AMPK-mTORC1-S6K1 signaling pathway, and protect against mutant huntingtin aggregation"],"prefix":"10.1007","volume":"64","author":[{"given":"Joanna","family":"Brokowska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Herman-Antosiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0478-3263","authenticated-orcid":false,"given":"Aleksandra","family":"Ha\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"issue":"21","key":"3539_CR1","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1093\/emboj\/19.21.5720","volume":"19","author":"Y Kabeya","year":"2000","unstructured":"Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T et al (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. 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