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Improved Antiulcer and Anticancer Properties of a trans-Resveratrol Analog in Mice▪
Improved Antiulcer and Anticancer Properties of a trans-Resveratrol Analog in Mice▪
- Source :
- The Journal of Pharmacology and Experimental Therapeutics; March 2009, Vol. 328 Issue: 3 p829-838, 10p
- Publication Year :
- 2009
-
Abstract
- Despite its potential, use of trans-resveratrol as an anticancer drug is severely constrained because of its tendency to prolong gastric ulceration. We found that in addition to delaying ulcer healing, trans-resveratrol also aggravated acute gastric ulceration induced by the nonsteroidal anti-inflammatory drugs by reducing the synthesis of prostaglandin (PG) E2via a specific inhibition of cyclooxygenase (COX)-1 that also hampered angiogenesis. However, for the first time, we showed that the 3′-5′-hydroxylated congener [(E)-HST-1] of trans-resveratrol, synthesized in multigram scale, exerted potential chemotherapeutic property but was nonulcerogenic in nature, rather moderately accelerated healing of indomethacin-induced gastric ulceration. HST-1 did not suppress COX-1, COX-2 expression, and PGE2synthesis but reduced the level of inflammatory myeloperoxidase (MPO) activity. The healing was augmented primarily through the nitric oxide synthase (NOS)-dependent pathway. HST-1 treatment induced endothelial NOS (eNOS) expression and reduced inducible NOS (iNOS), resulting in increased eNOS/iNOS ratio. The selective iNOS inhibitor [l-N6-(1-iminoethyl) lysine hydrochloride] and nonselective NOS inhibitor (Nω-nitro-l-arginine methyl ester) treatment revealed that eNOS could be the probable molecular switch to accelerate the indomethacin-induced ulcer healing in HST-1-treated mice. Furthermore, the anticancer effect of HST-1 on U937 and K562 leukemia cell lines was found to be significantly better than that of trans-resveratrol. Overall, these established HST-1 as a potentially better anticancer compound than trans-resveratrol, considering it is devoid of any ulcerogenic side effects. In conclusion, for the first time, we showed that a novel analog of trans-resveratrol, HST-1, was devoid of ulcerogenic adversative effects of trans-resveratrol but retained potentially better anticancer property.
Details
- Language :
- English
- ISSN :
- 00223565 and 15210103
- Volume :
- 328
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- The Journal of Pharmacology and Experimental Therapeutics
- Publication Type :
- Periodical
- Accession number :
- ejs68398524
- Full Text :
- https://doi.org/10.1124/jpet.108.145334