**2. Chemistry of curcumin**

For thousands of years, plants and some parts of animal have been used as dietary agents which have been identified to be biologically active. These natural compounds have gained considerable interest for their potential as treatment and preventive agents for human diseases. Curcumin (diferuloylmethane) is a major biologically active compound extracted from the dried rhizome of turmeric or *Curcuma longa*. It has been widely used for centuries as medicinal plant and food additive due to its yellow color. Its medicinal properties are attributed to curcuminoids, which include curcumin (curcumin I), demethoxycurcumin (curcumin II), and bisdemethoxycurcumin (curcumin III) (Figure 2). Curcumin I (77%) is a

Fig. 2. Chemical structure of curcuminoids

major component found in commercial curcumin, while curcumin II and III constitute approximately 17% and 3% respectively. Cucumin is a water-insoluble compound, but

Anticancer Properties of Curcumin 349

oncogenes such as myc and ras or impede the function of tumor suppressor genes such as p53 (Vogelstein and Kinzler, 2004). Curcumin has been shown to suppress oncogenes and activate tumor suppressor genes in various cancer cell types (Table 1). In an *in vivo* study, curcumin suppresses c-fos and c-Ha-ras activation induced by environmental mutagenic agents (Limtrakul et al., 2001). Dietary administration of curcumin (0.1-0.2%) prevents 2 dimethylbenz(α)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumor in mice. There is an increase in the oncogene (c-fos and ras) expression in this tumor model, which is suppressed by the dietary curcumin. Similarly, c-myc is also a target oncogene

attenuated by curcumin in the TPA-induced tumor model (Kakar and Roy, 1994).

Chemopreventive properties Cancer Carcinogen Animal References

Stomach cancer MNNG Rat Ikesaki et al., 2001 Colon cancer DMH Rat Devasena et al., 2003 Papilloma 2-AAF - Anto et al., 1996 Mammary tumor DMBA Rat Pereira et al., 1996 Skin tumor TPA Mouse Lu et al., 1993

Liver cancer Diethylnitrosamine Mouse Chuang et al., 2000

B cell lymphoma Suppress c-myc Han et al., 1999 Mouse skin cancer Suppress c-myc activated by TPA Kakar & Roy, 1994

adenocarcinoma Enhance p53 activity Song et al., 2005

Human glioma Enhance p53 activity Liu et al., 2007

Human breast cancer Enhance p53 activity Choudhuri et al., 2002

lymphoma Inhibit constitutive NF-B activation Shishodia et al., 2005 Mouse melanoma Inhibit constitutive NF-B activation Marin et al., 2007 Human oral cancer Inhibit constitutive NF-B activation Sharma et al., 2006

Inhibit constitutive NF-B activation

Anti-inflammation -related cancer Cancer Mechanism References


and COX expression Shishodia et al., 2003

Skin tumor Suppress c-fos and c-Ha-ras-

Table 1. Cancer preventive properties of curcumin

Human colon

Human mantle cell

Non-small cell lung

carcinoma

Oncogene suppression and tumor suppressor gene activation Cancer Mechanism References

activation by DMBA Limtrakul et al., 2001

dissolves well in ethanol, dimethylsulfoxide, and other organic solvents. The molecular weight of curcumin is 368.37 and melting point is 183 °C. It shows a spectrophotometric maximum absorption (λmax) at 450 nm in methanol (Prasad and Sarasija, 1997). Fluorescence of curcumin occurs at 524 nm in acetonitrile and 549 nm in ethanol (Chignell et al., 1994). Curcumin undergoes rapid degradation in phosphate buffer and serum-free media, i.e., 90% within 30 minutes (Wang et al., 1997). In serum-containing (10%) media and human blood, curcumin is more stable with less than 20% degradation in 1 hour, and about 50% after 8 hours. Its degradation products are *trans*-6-(4′-hydroxy-3′-methoxyphenyl)-2,4-dioxo-5 hexenal (major) and vanillin, ferulic acid, and feruloyl methane (minor) (Wang et al., 1997).
