These authors contributed equally to this work.
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
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 55, Issue 11, pages 1646–1654, November 2011
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
- 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
- National Science Council NSC. Grant Numbers: 98-2313-B-022-002-MY3, 98-2321-B-022-001, 100-2918-I-022-005
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.