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Curcumin Induces Cross-Regulation Between Autophagy and Apoptosis in Uterine Leiomyosarcoma Cells
  1. Bin Li, MD, PhD,
  2. Takashi Takeda, MD, PhD*,,
  3. Kenji Tsuiji, PhD,
  4. Tze Fang Wong, MD, PhD,
  5. Mari Tadakawa, MD,
  6. Akiko Kondo, MD, PhD,
  7. Satoru Nagase, MD, PhD and
  8. Nobuo Yaegashi, MD, PhD
  1. *Division of Women’s Health, Research Institute of Traditional Asian Medicine, Kinki University School of Medicine, Osaka; and
  2. Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  1. 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: take{at}med.kindai.ac.jp.

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.

  • Uterine LMS
  • Curcumin
  • Autophagy
  • Apoptosis
  • ERK1/2

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Footnotes

  • 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.

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