Curcumin (diferuloyl methane) Benefits
Curcumin (diferuloyl methane), is a major component of Curcuma species, which is
commonly used as a yellow coloring and flavoring agent in foods.
Curcuminoids, a group of phenolic compounds isolated from the roots of Curcuma longa (Zingiberaceae),
exhibit a variety of beneficial effects on health and on events that help in preventing certain diseases. [10]

Curcumin has been widely used for centuries in the Asian countries without any toxic effects. [6] Epidemiological
data also suggest that curcumin may be responsible for the lower rate of colorectal cancer in these countries.
[6] Curcumin is a naturally occurring powerful anti-inflammatory medicine and some researchers suggested to
use curcumin as an agent to reverse or inhibit the malignant transformation of colon cancer cells and to prevent
invasion and metastasis*. [11]

*More studies are needed to support this suggestion.

CURCUMIN FUNCTIONAL STRUCTURE

Analysis of curcumin (diferuloylmethane)  structure revealed the presence of beta-diketone moiety and phenolic
hydroxy groups that were believed to contribute to antioxidation. [8]

ANTI-CANCER ACTIVITIES

Curcumin has shown anti-carcinogenic activity in animals as indicated by its ability to block colon tumor
initiation by azoxymethane and skin tumor promotion induced by phorbol ester
12-O-tetradecanoylphorbol-13-acetate (TPA). The structurally related compounds chlorogenic acid, caffeic acid
and ferulic acid are less potent inhibitors on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor
promotion in mouse skin.  Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive
oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and
inducible nitric oxide synthase. Curcumin is also a potent inhibitor of protein kinase C, EGF-receptor tyrosine
kinase and IkappaB kinase. Subsequently, curcumin inhibits the activation of NFkappaB and the expressions of
c-jun, c-fos, c-myc and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking
signal transduction pathways in the target cells. [1,2, 5]

MORE DETAILS Curcumin inhibits lipooxygenase activity and is a specific inhibitor of cyclooxygenase-2
expression. Curcumin inhibits the initiation of carcinogenesis by inhibiting the cytochrome P-450 enzyme activity
and increasing the levels of glutathione-S-transferase. Curcumin inhibits the promotion/progression stages of
carcinogenesis. The anti-tumor effect of curcumin has been attributed in part to the arrest of cancer cells in S,
G2/M cell cycle phase and induction of apoptosis. [6]

In a study, when mouse fibroblast cells were treated with TPA alone, PKC translocated from the cytosolic
fraction to the particulate fraction. Treatment with 15 or 20 microM curcumin for 15 min inhibited TPA-induced
protein kinase C activity in the particulate fraction by 26-60%. Curcumin also inhibited protein kinase C activity in
vitro by competing with phosphatidylserine. Curcumin (10 microM) suppressed the expression of c-jun in
TPA-treated cells. [3]

Commercial curcumin isolated from the rhizome of the plant Curcuma longa Linn contains 3 major
curcuminoids (approximately 77% curcumin, 17% demethoxycurcumin, and 3% bisdemethoxycurcumin). [4]

Commercial curcumin, pure curcumin, and demethoxycurcumin are about equipotent as inhibitors of
TPA-induced tumor promotion in mouse skin, whereas bisdemethoxycurcumin is somewhat less active. Topical
application of curcumin inhibits tumor initiation by benzo[a]pyrene and tumor promotion by TPA in mouse skin.
Dietary curcumin (commercial grade) inhibits benzo[a]pyrene -induced stomach cancer,
N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)-induced duodenal cancers, and azoxymethane (AOM)-induced
colon cancers. [4]

SPECULATION Cystic fibrosis (CF), the most-common lethal hereditary disease in the white population, is
caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The mutation
that is most frequently responsible for the disease, DeltaF508, causes misfolding and retention of the CFTR
protein in the endoplasmic reticulum. This leads to a series of cellular dysfunctions and results in a multi-organ
disease. The activation of mutant forms of the cystic fibrosis transmembrane conductance regulator (CFTR),
particularly the most frequent mutant allele (DeltaF508), is a potential strategy for the treatment of the disease
cystic fibrosis (CF). Scientists are interested to find if curcumin is able to restore function to this allele, both in
heterologous expression systems and in DeltaF508 CF mice. [12, 13]

TOXICITY AND SAFETY

A phase 1 human trial with 25 subjects using up to 8000 mg of curcumin per day for 3 months found no toxicity
from curcumin. Five other human trials using 1125-2500 mg of curcumin per day have also found it to be safe.
[7] Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. [9]

METABOLISM

Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds
subsequently were converted to monoglucuronide conjugates (in an animal study). [5]

SUGGESTED READING

Lin JK Suppression of protein kinase C and nuclear oncogene expression as possible action mechanisms of
cancer chemoprevention by Curcumin. Arch Pharm Res. 2004 Jul;27(7):683-92.

Duvoix A Chemopreventive and therapeutic effects of curcumin. Cancer Lett. 2005 Jun 8;223(2):181-90. Epub
2004 Nov 11

Karunagaran D et al Induction of apoptosis by curcumin and its implications for cancer therapy. Curr Cancer
Drug Targets. 2005 Mar;5(2):117-29.

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REFERENCES

[1] Conney AH et al, Inhibitory effect of curcumin and some related dietary compounds on tumor promotion and arachidonic
acid metabolism in mouse skin. Adv Enzyme Regul. 1991;31:385-96. [2] Conney AH et al, Some perspectives on dietary
inhibition of carcinogenesis: studies with curcumin and tea. Proc Soc Exp Biol Med. 1997 Nov;216(2):234-45. [3] Lin JK et al
Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer
chemoprevention by apigenin and curcumin. J Cell Biochem Suppl. 1997;28-29:39-48 [4] Huang MT et al, Inhibitory effects of
curcumin on tumorigenesis in mice. J Cell Biochem Suppl. 1997;27:26-34. [5] Lin JK et al, Recent studies on the biofunctions
and biotransformations of curcumin. Biofactors. 2000;13(1-4):153-8. [6] Chauhan DP et al Chemotherapeutic potential of
curcumin for colorectal cancer., Curr Pharm Des. 2002;8(19):1695-706. [7] Chainani-Wu N Safety and anti-inflammatory activity
of curcumin: a component of tumeric (Curcuma longa). J Altern Complement Med. 2003 Feb;9(1):161-8. [8] Leu TH The
molecular mechanisms for the antitumorigenic effect of curcumin. Curr Med Chem Anti-Canc Agents. 2002 May;2(3):357-70. [9]
Aggarwal BB Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 2003 Jan-Feb;23(1A):363-98.
[10] Joe B et al Biological properties of curcumin-cellular and molecular mechanisms of action. Crit Rev Food Sci Nutr.
2004;44(2):97-111. [11] Narayan S Curcumin, a multi-functional chemopreventive agent, blocks growth of colon cancer cells by
targeting beta-catenin-mediated transactivation and cell-cell adhesion pathways. J Mol Histol. 2004 Mar;35(3):301-7. [12] Davis
PB et al, Some like it hot: curcumin and CFTR. Trends Mol Med. 2004 Oct;10(10):473-5. [13] Mall M Correction of the CF defect
by curcumin: hypes and disappointments. Bioessays. 2005 Jan;27(1):9-13.
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