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Novel podophyllotoxin and benzothiazole derivative induces transitional morphological and functional changes in HaCaT cells

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dc.abstract.enPodophyllotoxin (PPT) is an antimitotic drug used topically in the treatment of anogenital warts. Due to its toxicity it cannot be administered systemically as an anticancer agent. However, modified PPT derivatives such as etoposide and teniposide are used clinically as systemic agents. Thus, we invented novel PPT derivative KL3 that was synthesized by photocyclization. Earlier we have shown that KL3 has an anticancer effect in various cell lines. Here we compared the toxicity of KL3 vs PPT on non-cancerous normal human keratinocytes (HaCaT) and peripheral blood mononuclear cells (PBMC) showing that KL3 is less toxic than PPT to non-cancerous cells. At concentrations that neither induced cell death, nor affected cell cycle, KL3 in HaCaT cells evoked transient ultrastructural features of ER stress, swelling of mitochondria and elongation of cytoplasmic processes. Those changes partially reversed with prolonged incubation while features of autophagy were induced. PPT in equivalent concentrations induced HaCaT cell death by cell cycle arrest, intrinsic apoptosis and finally disintegration of cell membranes followed by secondary necrosis. In conclusion, we show that the KL3 derivative of PPT in contrast to PPT allows repair of normal keratinocytes and triggers mechanisms that restore non-tumor cell homeostasis
dc.affiliationUniwersytet Warszawski
dc.contributor.authorStrus, Piotr
dc.contributor.authorSzczepankiewicz, Andrzej
dc.contributor.authorWojcik, Cezary
dc.contributor.authorBorensztejn, Karol
dc.contributor.authorLisiecki, Kamil
dc.contributor.authorBialy, Lukasz P.
dc.contributor.authorMlynarczuk-Bialy, Izabela
dc.contributor.authorNIEZNAŃSKA, HANNA
dc.contributor.authorCzarnocki, Zbigniew
dc.date.accessioned2024-01-25T13:52:34Z
dc.date.available2024-01-25T13:52:34Z
dc.date.copyright2021-03-12
dc.date.issued2021
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.versionFINAL_PUBLISHED
dc.description.volume73
dc.identifier.doi10.1016/J.TIV.2021.105144
dc.identifier.issn0887-2333
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/113964
dc.identifier.weblinkhttp://www.journals.elsevier.com/
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofToxicology in Vitro
dc.relation.pagesart.no. 105144
dc.rightsCC-BY-NC-SA
dc.sciencecloudnosend
dc.subject.enPodophyllotoxin
dc.subject.enBenzothiazole
dc.subject.enKeratinocytes
dc.subject.enCell death
dc.subject.enApoptotic caspase 9
dc.subject.enHaCaT ultrastructure in TEM
dc.titleNovel podophyllotoxin and benzothiazole derivative induces transitional morphological and functional changes in HaCaT cells
dc.typeJournalArticle
dspace.entity.typePublication