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

通过将姜黄素与黄酮类化合物槲皮素和非瑟酮相结合,可实现特定的不可逆细胞周期停滞和癌细胞耗竭

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作者:Viviana Barra, Roberta Flavia Chiavetta, Simona Titoli, Ivana Maria Provenzano, Pietro Salvatore Carollo, Aldo Di Leonardo

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.

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.

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.

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