Mechanism of inhibition of benzo[a]pyrene-induced forestomach cancer in mice by dietary curcumin

Shivendra V. Singh, Xun Hu, Sanjay K. Srivastava, Manish Singh, Hong Xia, John L. Orchard, Howard A. Zaren

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Curcumin (diferuloylmethane), the major yellow pigment in turmeric, has been shown to inhibit benzo[a]pyrene (BaP)-induced forestomach cancer in mice through mechanism(s) not fully understood. It is well known that while cytochrome P4501A1 (CYP1A1) and epoxide hydrolase (EH) are important in the conversion of BaP to its activated form, (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BaPDE], the detoxification of (+)-anti-BaPDE is accomplished by glutathione (GSH) S-transferases (GST). Therefore, it seems reasonable to postulate that curcumin may exert anti-carcinogenic activity either by inhibiting activation of BaP or (and) by enhancing the detoxification of (+)-anti-BaPDE. Administration p.o. of 2% curcumin in the diet to female A/J mice for 14 days, which has been shown to cause a significant inhibition in BaP-induced forestomach tumorigenesis, resulted in a modest but statistically significant reduction in hepatic ethoxyresorufin O-deethylase (EROD) activity, a reaction preferentially catalyzed by CYP1A1. While EROD activity could not be detected in the forestomach of either control or treated mice, curcumin feeding caused a statistically significant increase (~ 2,3-fold) in hepatic EH and GST activities. Hepatic and forestomach GSH levels, and forestomach EH and GST activities were not affected by curcumin treatment. Even though the levels of various hepatic GST isoenzymes were significantly increased upon curcumin feeding, maximum induction was noticed for the pi class isoenzyme (mGSTP1-1), which among murine hepatic GSTs is highly efficient in the detoxification of (+)-anti-BaPDE. In conclusion, the results of the present study suggest that curcumin may inhibit BaP-induced forestomach cancer in mice by affecting both activation as well as inactivation pathways of BaP metabolism in the liver.

Original languageEnglish (US)
Pages (from-to)1357-1360
Number of pages4
JournalCarcinogenesis
Volume19
Issue number8
DOIs
StatePublished - Aug 1 1998

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Curcumin
Benzo(a)pyrene
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
Epoxide Hydrolases
Liver
Neoplasms
Transferases
Carboxylesterase
Cytochrome P-450 CYP1A1
Cytochromes
Isoenzymes
Curcuma
Glutathione Transferase
Carcinogenesis
Diet

ASJC Scopus subject areas

  • Cancer Research

Cite this

Singh, S. V., Hu, X., Srivastava, S. K., Singh, M., Xia, H., Orchard, J. L., & Zaren, H. A. (1998). Mechanism of inhibition of benzo[a]pyrene-induced forestomach cancer in mice by dietary curcumin. Carcinogenesis, 19(8), 1357-1360. https://doi.org/10.1093/carcin/19.8.1357

Mechanism of inhibition of benzo[a]pyrene-induced forestomach cancer in mice by dietary curcumin. / Singh, Shivendra V.; Hu, Xun; Srivastava, Sanjay K.; Singh, Manish; Xia, Hong; Orchard, John L.; Zaren, Howard A.

In: Carcinogenesis, Vol. 19, No. 8, 01.08.1998, p. 1357-1360.

Research output: Contribution to journalArticle

Singh, SV, Hu, X, Srivastava, SK, Singh, M, Xia, H, Orchard, JL & Zaren, HA 1998, 'Mechanism of inhibition of benzo[a]pyrene-induced forestomach cancer in mice by dietary curcumin', Carcinogenesis, vol. 19, no. 8, pp. 1357-1360. https://doi.org/10.1093/carcin/19.8.1357
Singh, Shivendra V. ; Hu, Xun ; Srivastava, Sanjay K. ; Singh, Manish ; Xia, Hong ; Orchard, John L. ; Zaren, Howard A. / Mechanism of inhibition of benzo[a]pyrene-induced forestomach cancer in mice by dietary curcumin. In: Carcinogenesis. 1998 ; Vol. 19, No. 8. pp. 1357-1360.
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