Skip Navigation LinksHome > June 2013 - Volume 23 - Issue 5 > Curcumin Induces Cross-Regulation Between Autophagy and Apop...
International Journal of Gynecological Cancer:
doi: 10.1097/IGC.0b013e31828c9581
Basic Science

Curcumin Induces Cross-Regulation Between Autophagy and Apoptosis in Uterine Leiomyosarcoma Cells

Li, Bin MD, PhD; Takeda, Takashi MD, PhD*†; Tsuiji, Kenji PhD; Wong, Tze Fang MD, PhD; Tadakawa, Mari MD; Kondo, Akiko MD, PhD; Nagase, Satoru MD, PhD; Yaegashi, Nobuo MD, PhD

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Abstract

Objective: Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapy. A natural occurring compound, curcumin, has been shown to have inhibitory effects on cancers. We previously demonstrated that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway and activating apoptosis. To further explore the anticancer effect of curcumin, we investigated the efficacy of curcumin on autophagy in LMS cells.

Methods: Cell proliferation in human uterine LMS cell lines, SKN and SK-UT-1, was assessed after exposure to rapamycin or curcumin. Autophagy was detected by Western blotting for light chain 3 and sequestosome 1 (SQSTM1/p62) expression. Apoptosis was confirmed by Western blotting for cleaved poly (ADP-ribose) polymerase (PARP).

Results: Both rapamycin and curcumin potently inhibited SKN and SK-UT-1 cell proliferation in a dose-dependent manner. Curcumin induced autophagy and apoptosis in SKN and SK-UT-1 cells, whereas rapamycin, a specific mTOR inhibitor, did not. Curcumin increased extracellular signal-regulated kinase 1/2 activity in both SKN and SK-UT-1 cells, whereas PD98059, an MEK1 inhibitor, inhibited both the extracellular signal-regulated kinase 1/2 pathway and curcumin-induced autophagy.

Conclusions: These experimental findings suggest that curcumin is a potent inhibitor of cell proliferation in uterine LMS and provide new insights about ongoing signaling events leading to the possible development of a new therapeutic agent.

Copyright © 2013 by IGCS and ESGO

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