International Journal of Clinical Oncology

, Volume 18, Issue 3, pp 380–388 | Cite as

Epigallocatechin-3-gallate potentiates curcumin’s ability to suppress uterine leiomyosarcoma cell growth and induce apoptosis

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

Abstract

Background

Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapeutic regimens. Two natural occurring compounds, curcumin and epigallocatechin gallate (EGCG), are reported to have anti-cancer activity. We previously reported that curcumin reduced uterine LMS cell proliferation by targeting the AKT–mTOR pathway. However, challenges remain in overcoming curcumin’s low bioavailability.

Methods

The human LMS cell line SKN was used. The effect of EGCG, curcumin or their combination on cell growth was detected by MTS assay. Their effect on AKT, mTOR, and S6 was detected by Western blotting. The induction of apoptosis was determined by Western blotting using cleaved-PARP specific antibody, caspase-3 activity and TUNEL assay. Intracellular curcumin level was determined by a spectrophotometric method. Antibody against EGCG cell surface receptor, 67-kDa laminin receptor (67LR), was used to investigate the role of the receptor in curcumin’s increased potency by EGCG.

Results

In this study, we showed that the combination of EGCG and curcumin significantly reduced SKN cell proliferation more than either drug alone. The combination inhibited AKT, mTOR, and S6 phosphorylation, and induced apoptosis at a much lower curcumin concentration than previously reported. EGCG enhanced the incorporation of curcumin. 67LR antibody partially rescued cell proliferation suppression by the combination treatment, but was not involved in the EGCG-enhanced intracellular incorporation of curcumin.

Conclusions

EGCG significantly lowered the concentration of curcumin required to inhibit the AKT–mTOR pathway, reduce cell proliferation and induce apoptosis in uterine LMS cells by enhancing intracellular incorporation of curcumin, but the process was independent of 67LR.

Keywords

Curcumin EGCG Uterine leiomyosarcoma mTOR AKT 67-kDa laminin receptor 

Notes

Acknowledgments

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

Conflict of interest

The authors have no conflict of interest.

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Copyright information

© Japan Society of Clinical Oncology 2012

Authors and Affiliations

  • Akiko Kondo
    • 1
  • Takashi Takeda
    • 1
    • 2
  • Bin Li
    • 2
  • Kenji Tsuiji
    • 2
  • Mari Kitamura
    • 1
  • Tze Fang Wong
    • 1
  • Nobuo Yaegashi
    • 1
    • 2
  1. 1.Department of Obstetrics and GynecologyTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Department of Traditional Asian MedicineTohoku University Graduate School of MedicineSendaiJapan

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