Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 55, Issue 11, Pages 1646-1654Publisher
WILEY
DOI: 10.1002/mnfr.201100454
Keywords
Autophagy; Curcumin; Tetrahydrocurcumin
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Funding
- National Science Council NSC [98-2313-B-022-002-MY3, 98-2321-B-022-001, 100-2918-I-022-005]
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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 3 beta 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.
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