1. 

 Cytotoxicity and cytoprotective activities of natural compounds.
The case of curcumin.
Xenobiotica, 1996,
vol. 26, no. 7, 667-680. JNM Commandeur et al.
 
   

Curcumin is described as a promising chemopreventive agent , which acts by blocking the process of chemically-induced toxicity at different levels.

The mechanism of chemopreventive action was determined in animal models.
Inhibition of the enzyme cytochrome P450A1 may explain the protective role of curcumin against benzopyrene(a)induced toxicity.

  
     
  2. Clinical Development Plan: Curcumin
Journal of Cellular Biochemistry 26S: 72-85 (1996).
Chemoprevention Branch and Agent Development Committee. 		 
   

The National Cancer Institute is currently developing curcumin as a drug for the treatment of cancer.

Plans for clinical studies include:

  • A Phase I trial assessing the safety and pharmacokinetics.
  • A Phase II chemoprevention trial on patients with oral leukoplakia and in cohorts at high risk for colon cancer.
 
 

Progress of the studies on curcumin sponsored/funded by NCI/DCPC
 
     
  3. Involvement of the beta-diketone moiety in the antioxidative mechanisms of tetrahydrocurcumin.
Biochem Pharmacol, 52(4): 519-25 1996 Aug 23. Y. Sugiyama et al.		  
   

This study validated the well-known superior antioxidant properties of tetrahydrocurcumin (THC) and explained the mechanism of antioxidant action
THC is a major metabolite of curcumin in the body. Both functional groups phenolic hydroxyl (1) and diketo (2) contribute to its antioxidant action.

 

  
 

 
     
  4.
Curcumin, a natural plant phenolic food additive, inhibits cell proliferation 
and induces cell cycle changes in colon adenocarcinoma cell lines by a prostaglandin-independent pathway.
J Lab Clin Med. 1997 Dec; 130(6): 576-584.
R. Hanif et al. 		 
   

In vitro studies on colon cancer cell lines revealed that the mechanism of chemopreventive action of curcumin is different from that of NSAIDs.

The antiproliferative effect of curcumin on these cells is not mediated through the inhibition of the production of arachidonic acid metabolites

 
     
  5. Inhibition of proliferation and apoptosis of human and rat T lymphocytes by curcumin, a curry pigment.
Biochem Pharmacol. 1997 Oct 15; 54(8): 899-907.
Sikora E, et al. 		 
   

In vitro studies performed on rat T lymphocytes and thymocytes revealed that curcumin inhibits their proliferation and apoptosis.

Curcumin has the capacity to inhibit both cell growth and cell death, implying that these processes share a common pathway.

At some point along this pathway, curcumin affects a common step. The authors presume that this involves a modulation of the AP-1 transcription factor.

 
       
  6. Inhibitory effect on curcumin on mammalian phosopholipase D activity.
FEBS Lett. 1997 Nov 10; 417(2): 196-198.
H. Yamamoto. et al . 		 
   

This study proposed that the chemopreventive action of Curcumin is partly due to the inhibition of the enzyme G-protein mediated phospholipase D.

 
       
  8. Some Perspectives on Dietary Inhibition of Carcinogenesis: Studies with Curcumin and Tea.
Dietary Chemicals and Cancer, 1997; pgs. 234-245.
AH Conney et al. 		 
   

The chemopreventive effects of curcumin were attributed toits effects on cellular differentiation, rather than to the inhibition of arachidonic acid metabolites. 

Although curcumin alone had no effect on cellular differentiation, when it was combined with all-trans retinoic acid or 1 alpha, 25-dihydroxyvitamin D3, a synergistic effect was observed.

 
       
  9. Nitric Oxide Scavenging by curcuminoids.
J Pharmacol. 1997, 49: 105-107.
Sreejayan and MNA Rao. 		 
   

Curcumin reduced the amount of nitrate formed by the reaction between oxygen and the nitric oxide generated from sodium nitroprusside.

Demethoxycurcumin, bisdemethoxycurcumin and diacetylcurcumin were as active as curcumin, showing that the methoxy and phenolic groups are not essential for the free radical scavenging action, including those towards nitric oxide

 
       
  10. Curcumin and Genistein, Plant Natural Products, Show Synergistic  Inhibitory Effects on the Growth of Human Breast Cancer MCF-7 Cells Induced by Estrogenic Pesticides.
Biochemical and Biophysical Research Communications 233, 692-696 (1997).
Surendra P Verma et al. 		 
   

When curcumin and genistein were added together in micromolar concentrations to estrogen -positive MCF-7 cells, there was a marked synergistic growth inhibitory effect.

These results suggest that a combination of curcumin and genistein in the diet may potentially reduce the proliferation of estrogen-positive human breast cells rendered cancerous by the action of pesticides or 17-beta estradiol.

 
       
  11. Kinetics of Alkaline Degradation of the Food Pigments Curcumin and Curcuminoids.
Journal of Food and Science. Volume 62, No. 2, 267-269 (1997).
Lisa C Price et al. 		 
   

The authors of this study observed that bisdemethoxycurcumin [BDMC] was less susceptible to degradation at pH 10.2 than curcumin [C] or demethoxycurcumin [DMC]. It was therefore recommended that BDMC be used in alkaline compositions to improve stability.

 
       
  12. Protective effect of Food Additives on Aflatoxin-induced mutagenicity and hepatocarcinogenicity.
Cancer Lett 1997 May 19; 115(2): 129-133.
KB Soni et al.		  
   

In a comparative study which examined the protective effects of various food additives on aflatoxin-induced mutagenicity and hepatocarcinogenicity, curcumin was found to offer the best protection.

Comparative efficacy of some natural compounds in inhibiting mutagenicity induced by Aflatoxin B1

 

  
 
 
       
  13. Amelioration of renal lesions associated with diabetes by dietary curcumin in streptozocin diabetic rats.
Mol Cell Biochem. 1998 Apr; 181(1-2): 87-96.
Suresh Babu P, et a l. 		 
   

In an animal model study, it was observed that dietary curcumin brought about significant inhibition in the progression of renal lesions.
Curcumin fed at 0.5% level in the diet to streptozotocin-induced diabetic rats for eight weeks lessened renal damage and preserved the integrity and functions of the kidneys.

 
       
  14. Curcumin and curcumin derivatives inhibit Tat-mediated transactivation of type 1 human   immunodeficiency virus long terminal repeat. 
Res Virol 1998 Jan; 149(1): 43-52.
Barthelemy S, et al. 		 
   

Tat protein secreted by HIV1 –infected cells is believed to have additional action in the pathogenesis of AIDS due to its ability to be taken up by non-infected cells as well.

In vitro studies revealed that Curcumin at concentrations of 10 to 100nM inhibited Tat transactivation by 70 to 80%.

 
       
  15. Mechanisms of anticarcinogenic properties of curcumin: the effect of curcumin on glutathione linked detoxification enzymes in rat liver.
Int J Biochem Cell Biol 1998 Apr; 30(4): 445-456.
JT Piper et al. 		 
   

Curcumin caused a dose-dependent induction of an isozyme which is known to detoxify a highly toxic product of lipid peroxidation, 4-hydroxynonenal.

These results suggest that the induction of enzymes involved in the detoxification of the electrophilic products of lipid peroxidation could explain the mechanism of action of curcumin as an anticancer and antiinflammatory agent.

  
       
  16. Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1, 2-dimethylhydrazine initiation.
Carcinogenesis vol 19, no 1, pp 81-85, 1998.
Jin Man Kim et al.		  
   

The comparative chemopreventive effects of carotenoids curcumin and tetrahydrocurcumin on the development of putative preneoplastic aberrant crypt foci in colons of mice, initiated with 1,2-dimethylhydrazine dihydrochloride (DMH) was studied.

 

 
   
 
       
  17. Joe, B., Lokesh, B.R. (1997) Effect of curcumin and capsaicin on arachidonic acid metabolism and lysosomal enzyme secretion by rat peritoneal macrophages. Lipids, 32(11):1173-80.
 
   

Rat peritoneal macrophages preincubated with 10 microM curcumin or capsaicin for 1 h inhibited the incorporation of arachidonic acid into membrane lipids, leukotriene B4 and leukotriene C4.

Curcumin and capsaicin also inhibited the secretion of collagenase, elastase, and hyaluronidase.

 
       
  18. Quantitation of chemopreventive synergism between (-)-epigallocatechin -3-gallate and curcumin in normal premalignant and malignant human oral epithelial cells.
Carcinogenesis vol 19, no 3, pp 419-424, 1998.
Avi Khafif et al. 		 
   

The synergistic chemopreventive effects of the potent antioxidant fraction from green tea (-) epigallocatechin gallate and curcumin was examined in an in vitro study on normal, premalignant and malignant human oral epithelial cells.

The effective doses required to inhibit the proliferation of cancer cells fell significantly when the antioxidants were used in combination.

  
       
  19. Protective Role of Curcumin in Ethanol Toxicity. Phytotherapy Research.
Vol 12, 55-56 (1998). V Rajakrishnan et al		  
   

Curcumin has protective effects against ethanol-induced liver toxicity as observed in a study on rats.

 
   

 
       
  20. Kawamori, T. (1999) Chemopreventive effect of curcumin,a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res , 59(3):597-601.
 
   

0.2% curcumin significantly inhibited colon tumorigenesis in treated rats as compared to untreated controls in a dose-dependent manner.

The authors confirmed that the chemopreventive activity of curcumin is observed when it is administered prior to, during and after carcinogen treatment as well as late in the premalignant stage of colon carcinogenes.

 
       
 
 

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