Share this article on:

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

International Journal of Gynecological Cancer: June 2013 - Volume 23 - Issue 5 - p 803–808
doi: 10.1097/IGC.0b013e31828c9581
Basic Science

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.

*Division of Women’s Health, Research Institute of Traditional Asian Medicine, Kinki University School of Medicine, Osaka; and †Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Address correspondence and reprint requests to Takashi Takeda, MD, PhD, Division of Women’s Health, Research Institute of Traditional Asian Medicine, Kinki University School of Medicine 377-2, Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. E-mail:

This work was supported, in part, by grants from the Japanese Ministry of Education, Science, Sports, and Culture, Tokyo, Japan (23592430).

The authors declare no conflicts of interest.

Received December 13, 2012

Accepted February 11, 2013

Copyright © 2013 by IGCS and ESGO