Curcumin induces permanent growth arrest of human colon cancer cells: Link between senescence and autophagy

Curcumin, a natural polyphenol derived from the rhizome of Curcuma longa, is a potent anticancer agent, which restricts tumor cells growth both in vitro and in vivo. Thus far curcumin was shown to induce death of cancer cells. This study reports induction of cellular senescence of human colon cancer HCT116 p53+/+ and p53-/- cells, human breast cancer MCF 7 cells and humanosteosarcoma U2OS cells upon curcumin treatment. The process of cellular senescence could be induced by treatment of cancer cells with different chemotherapeutics and is observed both in vitro and in vivo. Moreover cellular senescence is considered to restrict tumor growth, thus it can be responsible for the efficacy of therapy.

Senescence of HCT116 cells was accompanied by autophagy, what was confirmed by electron microscopy observations of autophagosomes in 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 and lead to increased number of proliferating cells.
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.

06 November 2012