title: Curcumin-treated cancer cells show mitotic disturbances leading to growth arrest and induction of senescence phenotype.
abstract: Cellular senescence is recognized as a potent anticancer mechanism that inhibits carcinogenesis. Cancer cells can also undergo senescence upon chemo- or radiotherapy. Curcumin, a natural polyphenol derived from the rhizome of Curcuma longa, shows anticancer properties both in vitro and in vivo. Previously, we have shown that treatment with curcumin leads to senescence of human cancer cells. Now we identified the molecular mechanism underlying this phenomenon. We observed a time-dependent accumulation of mitotic cells upon curcumin treatment. The time-lapse analysis proved that those cells progressed through mitosis for a significantly longer period of time. A fraction of cells managed to divide or undergo mitotic slippage and then enter the next phase of the cell cycle. Cells arrested in mitosis had an improperly formed mitotic spindle and were positive for γH2AX, which shows that they acquired DNA damage during prolonged mitosis. Moreover, the DNA damage response pathway was activated upon curcumin treatment and the components of this pathway remained upregulated while cells were undergoing senescence. Inhibition of the DNA damage response decreased the number of senescent cells. Thus, our studies revealed that the induction of cell senescence upon curcumin treatment resulted from aberrant progression through the cell cycle. Moreover, the DNA damage acquired by cancer cells, due to mitotic disturbances, activates an important molecular mechanism that determines the potential anticancer activity of curcumin.
authors.affiliation: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland. Electronic address: g.mosieniak@nencki.gov.pl.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Mosieniak
authors.affiliation: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland.
authors.forename: Małgorzata A
authors.initials: MA
authors.lastname: Sliwinska
authors.affiliation: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Przybylska
authors.affiliation: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland.
authors.forename: Wioleta
authors.initials: W
authors.lastname: Grabowska
authors.affiliation: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Sunderland
authors.affiliation: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bielak-Zmijewska
authors.affiliation: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sikora
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008938:Mitosis / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D003474:Curcumin
keywords: Cancer; Curcumin; DNA damage; Mitotic arrest; Senescence