Effects of Stable Degradation Products of Curcumin on Cancer Cell Proliferation and Inflammation

Article abstract of DOI:10.1021/acs.jafc.6b04343

Curcumin is among the most promising dietary compounds for cancer prevention. However, curcumin rapidly degrades in aqueous buffer at physiological pH, making it difficult to understand whether the effects of curcumin are from curcumin itself or its degradation products. Here we studied the antiproliferative and anti-inflammatory effects of curcumin degradation products, including its total degradation products (a mixture containing all stable degradation products of curcumin) and bicyclopentadione (a dominant stable degradation compound of curcumin). Curcumin potently modulated cell proliferation, progression of cell cycle, and apoptosis in MC38 colon cancer cells and inhibited lipopolysaccharide (LPS)-induced inflammatory responses and NF-κB signaling in RAW 264.7 macrophage cells. In contrast, neither the total degradation products of curcumin nor bicyclopentadione had such effects. For example, after 24 h of treatment in MC38 colon cancer cells, 5 μg/mL curcumin inhibited 39.2 ± 1.8% of cell proliferation, whereas its degradation products were inactive. Together, these results suggest that the stable chemical degradation products of curcumin are not likely to play a major role in mediating the biological activities of curcumin.

Full text of DOI:10.1021/acs.jafc.6b04343

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Article
Effects of stable degradation products of curcumin
on cancer cell proliferation and inflammation
Katherine Z. Sanidad, Julia Zhu, Weicang Wang, Zheyuan Du, and Guodong Zhang
J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.6b04343 • Publication Date (Web): 11 Nov 2016
Downloaded from http://pubs.acs.org on November 14, 2016
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Journal of Agricultural and Food Chemistry
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Effects of Stable Degradation Products of Curcumin on Cancer Cell Proliferation and
Inflammation
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Katherine Z. Sanidad 1,2, *, Julia Zhu 1, *, Weicang Wang 1, Zheyuan Du 1, and Guodong Zhang
1,#
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1 Department of Food Science, 2 Molecular and Cellular Biology Graduate Program, University
of Massachusetts, Amherst, MA, USA
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# To whom correspondence should be addressed: Guodong Zhang, Department of Food
Science, University of Massachusetts, Amherst, MA, USA. Email: guodongzhang@umass.edu,
Tel: 413ꢀ4541014, Fax: 413ꢀ5451262
* K.Z.S. and J.Z. contributed equally to this work.
Title running head: Curcumin degradation
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Abstract
Curcumin is among the most promising dietary compounds for cancer prevention. However,
curcumin rapidly degrades in aqueous buffer at physiological pH, making it difficult to
understand whether the effects of curcumin are from curcumin itself or its degradation products.
Here we studied the antiꢀproliferative and antiꢀinflammatory effects of curcumin degradation
products, including its total degradation products (a mixture containing all stable degradation
products of curcumin) and bicyclopentadione (a dominant stable degradation compound of
curcumin). Curcumin potently modulated cell proliferation, progression of cell cycle, and
apoptosis in MC38 colon cancer cells, and inhibited lipopolysaccharide (LPS)ꢀinduced
inflammatory responses and NFꢀkB signaling in RAW 264.7 macrophage cells. In contrast,
neither the total degradation products of curcumin nor bicyclopentadione had such effects. For
example, after 24ꢀh treatment in MC38 colon cancer cells, 5 ꢁg/mL curcumin inhibited 39.2±1.8%
of cell proliferation, while its degradation products were inactive. Together, these results
suggest that the stable chemical degradation products of curcumin are not likely to play a major
role in mediating the biological activities of curcumin.
Keywords
Curcumin; degradation; bicyclopentadione; cancer; inflammation
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Introduction
Curcumin is among the most promising dietary compounds for cancer prevention and treatment
1. Animal studies have shown that curcumin inhibits many types of cancers, including but not
limited to pancreatic cancer 2, breast cancer 3, cervical cancer 4, lung cancer 5, and colorectal
cancer 6. Human studies also support the antiꢀcancer effects of curcumin. One Phase IIα human
clinical trial has shown that a daily intake of 4 grams of curcumin for a month caused a ~40%
reduction of aberrant crypt foci, a biomarker of colorectal cancer 7. Another Phase II human
clinical trial has shown that a daily intake of 8 grams of curcumin displayed antiꢀcancer efficacy
in some patients with advanced pancreatic cancer 8. Currently the antiꢀcancer effects of
curcumin are being evaluated in many human clinical trials.
Until now, the molecular mechanisms of curcumin are not well understood. Recent studies
showed that curcumin has a poor chemical stability at physiological pH: in aqueous solution at
physiological pH, it has a halfꢀlife of several minutes, thus leading to the formation of various
degradation products 9, 10. These chemical degradation products include two classes of
compounds: (1) alkaline hydrolysis products, where the hydroxyl ion (OHꢀ) attacks the carbonyl
group of curcumin, generating hydrolyzed products such as ferulic acid, vanillin, ferulaldehyde,
and feruloyl methane 11; and (2) autoxidation products, where curcumin is first converted to a
phenolic radical, which then migrates to the conjugated heptadienedione chain and initiates a
chain reaction of curcumin degradation to generate cyclized compounds such as
bicyclopentadione (BCP) 9, 10, 12. Recent studies showed that the alkaline hydrolysis products are
minor compounds of curcumin degradation products, and the autoxidation pathway is the
dominant mechanism to mediate curcumin degradation 9, 10, 12. When curcumin was added into
mouse macrophage RAW 264.7 cells, the cellular level of BCP was increased by 1.8ꢀfold,
suggesting that chemical degradation could happen in biological systems 13. Because of the
short halfꢀlife of curcumin at physiological pH, it is difficult to understand whether the observed
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