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Article

Specific Irreversible Cell-Cycle Arrest and Depletion of Cancer Cells Obtained by Combining Curcumin and the Flavonoids Quercetin and Fisetin

Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 90128 Palermo, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Maciej Wnuk
Genes 2022, 13(7), 1125; https://doi.org/10.3390/genes13071125
Received: 2 May 2022 / Revised: 13 June 2022 / Accepted: 21 June 2022 / Published: 23 June 2022
(This article belongs to the Section Molecular Genetics and Genomics)
Background: Induced senescence could be exploited to selectively counteract the proliferation of cancer cells and target them for senolysis. We examined the cellular senescence induced by curcumin and whether it could be targeted by fisetin and quercetin, flavonoids with senolytic activity. Methods: Cell-cycle profiles, chromosome number and structure, and heterochromatin markers were evaluated via flow cytometry, metaphase spreads, and immunofluorescence, respectively. The activation of p21waf1/cip1 was assessed via RT-qPCR and immunoblotting. Senescent cells were detected via SA-β-Galactosidase staining. Results: We report that curcumin treatment specifically triggers senescence in cancer cells by inducing mitotic slippage and DNA damage. We show that curcumin-induced senescence is p21waf1/cip1-dependent and characterized by heterochromatin loss. Finally, we found that flavonoids clear curcumin-induced senescent cancer cells. Conclusions: Our findings expand the characterization of curcumin-induced cellular senescence in cancer cells and lay the foundation for the combination of curcumin and flavonoids as a possible anti-cancer therapy. View Full-Text
Keywords: senescence; curcumin; senolytics; heterochromatin; DNA methylation; H3K9 trimethylation; SAHF; fisetin; quercetin senescence; curcumin; senolytics; heterochromatin; DNA methylation; H3K9 trimethylation; SAHF; fisetin; quercetin
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MDPI and ACS Style

Barra, V.; Chiavetta, R.F.; Titoli, S.; Provenzano, I.M.; Carollo, P.S.; Di Leonardo, A. Specific Irreversible Cell-Cycle Arrest and Depletion of Cancer Cells Obtained by Combining Curcumin and the Flavonoids Quercetin and Fisetin. Genes 2022, 13, 1125. https://doi.org/10.3390/genes13071125

AMA Style

Barra V, Chiavetta RF, Titoli S, Provenzano IM, Carollo PS, Di Leonardo A. Specific Irreversible Cell-Cycle Arrest and Depletion of Cancer Cells Obtained by Combining Curcumin and the Flavonoids Quercetin and Fisetin. Genes. 2022; 13(7):1125. https://doi.org/10.3390/genes13071125

Chicago/Turabian Style

Barra, Viviana, Roberta F. Chiavetta, Simona Titoli, Ivana M. Provenzano, Pietro S. Carollo, and Aldo Di Leonardo. 2022. "Specific Irreversible Cell-Cycle Arrest and Depletion of Cancer Cells Obtained by Combining Curcumin and the Flavonoids Quercetin and Fisetin" Genes 13, no. 7: 1125. https://doi.org/10.3390/genes13071125

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