These authors contributed equally to this work.
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Research Article
Tetrahydrocurcumin, a major metabolite of curcumin, induced autophagic cell death through coordinative modulation of PI3K/Akt-mTOR and MAPK signaling pathways in human leukemia HL-60 cells
Article first published online: 19 SEP 2011
DOI: 10.1002/mnfr.201100454
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Wu, J.-C., Lai, C.-S., Badmaev, V., Nagabhushanam, K., Ho, C.-T. and Pan, M.-H. (2011), Tetrahydrocurcumin, a major metabolite of curcumin, induced autophagic cell death through coordinative modulation of PI3K/Akt-mTOR and MAPK signaling pathways in human leukemia HL-60 cells. Mol. Nutr. Food Res., 55: 1646–1654. doi: 10.1002/mnfr.201100454
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These authors contributed equally to this work.
Publication History
- Issue published online: 2 NOV 2011
- Article first published online: 19 SEP 2011
- Manuscript Accepted: 9 AUG 2011
- Manuscript Revised: 29 JUL 2011
- Manuscript Received: 7 JUL 2011
Funded by
- National Science Council NSC. Grant Numbers: 98-2313-B-022-002-MY3, 98-2321-B-022-001, 100-2918-I-022-005
- Abstract
- Article
- References
- Cited By
Keywords:
- Autophagy;
- Curcumin;
- Tetrahydrocurcumin
Abstract
Scope: Autophagy (type II programmed cell death) is crucial for maintaining cellular homeostasis. Several autophagy-deficient or knockout studies indicate that autophagy is a tumor suppressor. Tetrahydrocurcumin (THC), a major metabolite of curcumin, has been demonstrated with anti-colon carcinogenesis and antioxidation in vivo.
Methods and results: In the present study, we found that treatment with THC induced autophagic cell death in human HL-60 promyelocytic leukemia cells by increasing autophage marker acidic vascular organelle (AVO) formation. Flow cytometry also confirmed that THC treatment did not increase sub-G1 cell population whereas curcumin did with strong apoptosis-inducing activity. At the molecular levels, the results from Western blot analysis showed that THC significantly down-regulated phosphatidylinositol 3-kinase/protein kinase B and mitogen-activated protein kinase signalings including decreasing the phosphorylation of mammalian target of rapamycin, glycogen synthase kinase 3β and p70 ribosomal protein S6 kinase. Further molecular analysis exhibited that the pretreatment of 3-methyladenine (an autophagy inhibitor) also significantly reduced acidic vascular organelle production in THC-treated cells.
Conclusion: Taken together, these results demonstrated the anticancer efficacy of THC by inducing autophagy as well as provided a potential application for the prevention of human leukemia.