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Curcumin enhances TRAIL-induced apoptosis of breast cancer cells by regulating apoptosis-related proteins

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Abstract

The TNF-related apoptosis inducing ligand (TRAIL) has promising anti-cancer therapeutic activity, although significant percentage of primary tumors resistant to TRAIL-induced apoptosis remains an obstacle to the extensive use of TRAIL-based mono-therapies. Natural compound curcumin could potentially sensitize resistant cancer cells to TRAIL. We found that the combination of TRAIL with curcumin can synergistically induces apoptosis in three TRAIL-resistant breast cancer cell lines. The mechanism behind this synergistic cell death was investigated by examining an effect of curcumin on the expression and activation of TRAIL-associated cell death proteins. Immunoblotting, RNA interference, and use of chemical inhibitors of TRAIL-activate signaling revealed differential effects of curcumin on the expression of Mcl-1 and activities of ERK and Akt. Curcumin-induced production of reactive oxygen species did not affect total expression of DR5 but it enhanced mobilization of DR5 to the plasma membrane. In these breast cancer cells curcumin also induced downregulation of IAP proteins. Taken together, our data suggest that a combination of TRAIL and curcumin is a potentially promising treatment for breast cancer, although the specific mechanisms involved in this sensitization could differ even among breast cancer cells of different origins.

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Acknowledgments

This research was supported by the Yujeonja-Donguibogam project based on Traditional herbs (Grant No. 2012M3A9C4048793), Republic of Korea, and by the International Research & Development Program of the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education, Science and Technology (MEST) of Korea (Grant No. NRF-2012K1A3A1A07045330), and by the Grant (2012-512) from the ASAN Institute for Life Sciences, Seoul, Korea.

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The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Asan Institute for Life Sciences, Asan Medical Center, Seoul, 138-736, Republic of Korea

    Sojung Park, Nayoung Suh & Inki Kim

  2. Department of Medicine, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea

    Nayoung Suh & Inki Kim

  3. Graduate School of East-West Medical Science, Kyung Hee University, Gyeonggi-do, Yongin, Republic of Korea

    Dong Hyung Cho

  4. Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 14220, Prague 4, Czech Republic

    Ladislav Andera

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  1. Sojung Park
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Correspondence to Inki Kim.

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Park, S., Cho, D.H., Andera, L. et al. Curcumin enhances TRAIL-induced apoptosis of breast cancer cells by regulating apoptosis-related proteins. Mol Cell Biochem 383, 39–48 (2013). https://doi.org/10.1007/s11010-013-1752-1

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