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International Journal of Clinical Oncology

Published in:

01-04-2014 | Original Article

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

Authors: Tze Fang Wong, Takashi Takeda, Bin Li, Kenji Tsuiji, Akiko Kondo, Mari Tadakawa, Satoru Nagase, Nobuo Yaegashi

Published in: International Journal of Clinical Oncology | Issue 2/2014

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.

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Title: Curcumin targets the AKT–mTOR pathway for uterine leiomyosarcoma tumor growth suppression
Authors: Tze Fang Wong
Takashi Takeda
Bin Li
Kenji Tsuiji
Akiko Kondo
Mari Tadakawa
Satoru Nagase
Nobuo Yaegashi
Publication date: 01-04-2014
Publisher: Springer Japan
Published in: International Journal of Clinical Oncology / Issue 2/2014
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-013-0563-4

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Abstract

Background

Methods

Results

Conclusion

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