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Despite intense research, little attention has been paid to scytophycin\u2010induced cell death or the structural features affecting its potency. We show that tolytoxin and its natural analogue, 7\u2010<jats:italic>O<\/jats:italic>\u2010methylscytophycin B, lacking the hydroxyl substitution in its macrolactone ring, differ substantially in their cytotoxic effect. Both compounds increase the level of caspases 3\/7, which are the main executioner proteases during apoptosis, in HeLa wild\u2010type (WT) cells. However, no caspase activity was detected in HeLa cells lacking Bax\/Bak proteins crucial for caspase activation via the mitochondrial pathway. Obtained data strongly suggests that scytophycins are capable of inducing mitochondria\u2010dependent apoptosis. These findings encourage further research in structure\u2010activity relationships in scytophycins and highlight the potential of these compounds in targeted drug delivery.<\/jats:p>","DOI":"10.1002\/cbic.202100489","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T11:44:59Z","timestamp":1637840699000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["New Insights into Tolytoxin Effect in Human Cancer Cells: Apoptosis Induction and the Relevance of Hydroxyl Substitution of Its Macrolide Cycle on Compound Potency"],"prefix":"10.1002","volume":"23","author":[{"given":"Kate\u0159ina","family":"Delawsk\u00e1","sequence":"first","affiliation":[{"name":"Institute of Microbiology of the Czech Academy of Sciences \u2013 Center Algatech  Novohradska 237 37981 Trebon Czech Republic"},{"name":"Faculty of Science, University of South Bohemia in \u010cesk\u00e9 Bud\u011bjovice  Brani\u0161ovsk\u00e1 1760 37005 \u010cesk\u00e9 Bud\u011bjovice Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Divok\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Microbiology of the Czech Academy of Sciences \u2013 Center Algatech  Novohradska 237 37981 Trebon Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Sedl\u00e1k","sequence":"additional","affiliation":[{"name":"CZ-OPENSCREEN: National Infrastructure for Chemical Biology Institute of Molecular Genetics of the ASCR, v.\u2005v.\u2005i.  142 20 Prague 4 Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marek","family":"Kuzma","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Structure Characterization Institute of Microbiology Academy of Sciences of the Czech Republic  Videnska 1083 142 20 Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumar","family":"Saurav","sequence":"additional","affiliation":[{"name":"Institute of Microbiology of the Czech Academy of Sciences \u2013 Center Algatech  Novohradska 237 37981 Trebon Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark\u00e9ta","family":"Macho","sequence":"additional","affiliation":[{"name":"Institute of Microbiology of the Czech Academy of Sciences \u2013 Center Algatech  Novohradska 237 37981 Trebon Czech Republic"},{"name":"Faculty of Science, University of South Bohemia in \u010cesk\u00e9 Bud\u011bjovice  Brani\u0161ovsk\u00e1 1760 37005 \u010cesk\u00e9 Bud\u011bjovice Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabor","family":"Steinbach","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Biological Research Center  6726 Temesv\u00e1ri krt. 62. 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