International Journal of Clinical Oncology

, Volume 19, Issue 2, pp 354–363 | Cite as

Curcumin targets the AKT–mTOR pathway for uterine leiomyosarcoma tumor growth suppression

  • Tze Fang Wong
  • Takashi Takeda
  • Bin Li
  • Kenji Tsuiji
  • Akiko Kondo
  • Mari Tadakawa
  • Satoru Nagase
  • Nobuo Yaegashi
Original Article

Abstract

Background

Uterine leiomyosarcomas generally do not respond well to standard chemotherapy. We previously demonstrated that curcumin, the active ingredient derived from the herb Curcuma longa, inhibits uterine leiomyosarcoma cells in vitro via the inhibition of the AKT–mammalian target of rapamycin (mTOR) pathway. As a preclinical investigation, we performed an in vivo study using female nude mice to confirm the therapeutic potential of curcumin against uterine leiomyosarcoma.

Methods

Human leiomyosarcoma cells, SK-UT-1, were inoculated in female nude mice to establish subcutaneous tumors. Either vehicle control or 250 mg/kg curcumin was administered intraperitoneally every day for 14 consecutive days, and the mice were then killed. The tumors were measured every 2–3 days. The tumors were processed for immunohistochemical analyses to detect total AKT, phosphorylated AKT, total mTOR, phosphorylated mTOR, and phosphorylated S6. To detect apoptosis, the tumors were stained for cleaved PARP and TUNEL. Ki-67 immunohistochemistry was performed to determine cell viability of the tumors.

Results

Compared with the control, curcumin reduced uterine leiomyosarcoma tumor volume and mass significantly with a concordant decrease in mTOR and S6 phosphorylation. However, AKT phosphorylation was not significantly altered. Cleaved PARP and TUNEL staining increased significantly with curcumin administration, indicating the induction of apoptosis. There was no difference in Ki-67 staining between the two groups.

Conclusion

Curcumin inhibited uterine leiomyosarcoma tumor growth in vivo by targeting the AKT–mTOR pathway for inhibition.

Keywords

Curcumin Uterine leiomyosarcoma AKT–mTOR pathway Apoptosis In vivo 

Notes

Acknowledgments

We thank Ms. Emi Endo, Ms. Etsuko Oba, and Ms. Etsuko Tomita for assistance in tissue processing and immunohistochemical analysis. This study was approved by the Ethics Committee for animal research and was supported by a Grant-in-aid from the Japanese Ministry of Education, Science, Sports, and Culture, Tokyo, Japan (23592430).

Conflict of interest

The authors report no conflict of interest.

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Copyright information

© Japan Society of Clinical Oncology 2013

Authors and Affiliations

  • Tze Fang Wong
    • 1
  • Takashi Takeda
    • 1
    • 2
  • Bin Li
    • 1
  • Kenji Tsuiji
    • 1
  • Akiko Kondo
    • 1
  • Mari Tadakawa
    • 1
  • Satoru Nagase
    • 1
  • Nobuo Yaegashi
    • 1
  1. 1.Department of Obstetrics and GynecologyTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Division of Women’s Health, Research Institute of Traditional Asian MedicineKinki University School of MedicineOsakaJapan

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