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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 547430, 11 pages
http://dx.doi.org/10.1155/2013/547430
Research Article

Resveratrol Downregulates Interleukin-6-Stimulated Sonic Hedgehog Signaling in Human Acute Myeloid Leukemia

1Department of Medicine, College of Medicine, Tzu Chi University, Hualien 97004, Taiwan
2Division of Hematology and Oncology, Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chiayi 62247, Taiwan
3Department of Biochemical Science and Technology, National Chiayi University, Chiayi 60004, Taiwan
4Department of Radiation Oncology, Columbia University, New York, NY 10027, USA
5Institute of Traditional Medicine, National Yang-Ming University, Taipei 11221, Taiwan

Received 15 December 2012; Accepted 15 January 2013

Academic Editor: Yu-Jen Chen

Copyright © 2013 Yu-Chieh Su et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

IL-6 and sonic hedgehog (Shh) signaling molecules are considered to maintain the growth of cancer stem cells (CSCs). Resveratrol, an important integrant in traditional Chinese medicine, possesses certain antitumor effects. However, the mechanisms on regulating acute myeloid leukemia (AML) are unclear. This study first used human subjects to demonstrate that the plasma levels of IL-6 and IL-1β in AML patients were higher and lower, respectively, than healthy donors. The expression of Shh preproproteins, and C- and N-terminal Shh peptides increased in bone marrow and peripheral blood mononuclear cells isolated from AML patients, and the plasma N-Shh secretion was greater. To further clarify the effect of IL-6 and resveratrol in Shh signaling, human AML HL-60 cells were tested. IL-6 upregulated Shh and Gli-1 expression and was accompanied by an increase of cell viability. Resveratrol significantly decreased CSC-related Shh expression, Gli-1 nuclear translocation, and cell viability in IL-6-treated HL-60 cells and had synergistic effect with Shh inhibitor cyclopamine on inhibiting cell growth. Conclusions. IL-6 stimulated the growth of AML cells through Shh signaling, and this effect might be blocked by resveratrol. Further investigations of Shh as a prognostic marker and resveratrol as a therapeutic drug target to CSCs in AML are surely warranted.