title: Curcumin induces permanent growth arrest of human colon cancer cells: link between senescence and autophagy.
abstract: Curcumin, a natural polyphenol derived from the rhizome of Curcuma longa, is a potent anticancer agent, which restricts tumor cell growth both in vitro and in vivo. Thus far curcumin was shown to induce death of cancer cells. This study reports the induction of cellular senescence of human colon cancer cells HCT116 upon curcumin treatment. The SA-β-galactosidase activation was observed both in p53+/+ and p53-/- cells, however the latter ones were less sensitive to the prosenescent activity of curcumin. Upregulation of p53 and p21 proteins was observed in p53+/+ HCT116, while p53-independent induction of p21 was noticed in p53-/- HCT116. Moreover, the senescence of HCT116 cells was accompanied by autophagy, that was confirmed by electron microscopy observations of autophagosomes in the curcumin-treated cells as well as LC3-II expression, punctue staining of LC3 and increased content of acidic vacuoles. Inhibition of autophagy, due to the diminished expression of ATG5 by RNAi decreased the number of senescent cells induced by curcumin, but did not lead to increased cell death. Altogether, we demonstrated a new antitumor activity of curcumin leading to cancer cell senescence and revealed the presence of a functional link between senescence and autophagy in curcumin-treated cells.
authors.affiliation: Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, PAS, 02-093 Warsaw, Poland. g.mosieniak@nencki.gov.pl
authors.forename: Grazyna
authors.initials: G
authors.lastname: Mosieniak
authors.forename: Marek
authors.initials: M
authors.lastname: Adamowicz
authors.forename: Olga
authors.initials: O
authors.lastname: Alster
authors.forename: Hubert
authors.initials: H
authors.lastname: Jaskowiak
authors.forename: Andrzej A
authors.initials: AA
authors.lastname: Szczepankiewicz
authors.forename: Grzegorz M
authors.initials: GM
authors.lastname: Wilczynski
authors.forename: Iwona A
authors.initials: IA
authors.lastname: Ciechomska
authors.forename: Ewa
authors.initials: E
authors.lastname: Sikora
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D000071187:Autophagy-Related Protein 5; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000473:pathology*; D003474:Curcumin / Q000494:pharmacology*; D020868:Gene Silencing; D045325:HCT116 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014617:Vacuoles / Q000187:drug effects; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C502778:ATG5 protein, human; D000970:Antineoplastic Agents; D000071187:Autophagy-Related Protein 5; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D001616:beta-Galactosidase; D003474:Curcumin