R
Roger
Guest
I never heard of this before (anybody know anything about ursolic acid?) but read the abstract below
and if you know anything about some of the things it suppresses (such as NF-kappaB, cox 2, and MMP-
9), you'll know it's probably a very potent anti-cancer agent (assuming it's safe to normal cells).
------
Cancer Res. 2003 Aug 1;63(15):4375-83.
Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through
suppression of IkappaBalpha kinase and p65 phosphorylation: correlation with down-regulation of
cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1.
Shishodia S, Majumdar S, Banerjee S, Aggarwal BB. Cytokine Research Laboratory, Department of
Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard,
Houston, TX 77030, USA.
The process of tumorigenesis requires cellular transformation, hyperproliferation, invasion,
angiogenesis, and metastasis. Several genes that mediate these processes are regulated by the
transcription factor nuclear factor-kappaB (NF-kappaB). The latter is activated by various
carcinogens, inflammatory agents, and tumor promoters. Thus, agents that can suppress NF-kappaB
activation have the potential to suppress carcinogenesis. Ursolic acid, a pentacyclic triterpene
acid, has been shown to suppress the expression of several genes associated with tumorigenesis, but
whether ursolic acid mediates its effects through suppression of NF-kappaB is not understood. In the
study described in the present report, we found that ursolic acid suppressed NF-kappaB activation
induced by various carcinogens including tumor necrosis factor (TNF), phorbol ester, okadaic acid,
H(2)O(2), and cigarette smoke. These effects were not cell type specific. Ursolic acid inhibited DNA
binding of NF-kappaB consisting of p50 and p65. Ursolic acid inhibited IkappaBalpha
degradation, IkappaBalpha phosphorylation, IkappaBalpha kinase activation, p65
phosphorylation, p65 nuclear translocation, and NF-kappaB-dependent reporter gene
expression. Ursolic acid also inhibited NF-kappaB-dependent reporter gene expression
activated by TNF receptor, TNF receptor-associated death domain, TNF receptor-associated
factor, NF-kappaB-inducing kinase, IkappaBalpha kinase, and p65. The inhibition of NF-kappaB
activation correlated with suppression of NF-kappaB-dependent cyclin D1, cyclooxygenase 2,
and matrix metalloproteinase 9 expression. Thus, overall, our results indicate that ursolic
acid inhibits IkappaBalpha kinase and p65 phosphorylation, leading to the suppression of NF-
kappaB activation induced by various carcinogens. These actions of ursolic acid may mediate
its antitumorigenic and chemosensitizing effects.
and if you know anything about some of the things it suppresses (such as NF-kappaB, cox 2, and MMP-
9), you'll know it's probably a very potent anti-cancer agent (assuming it's safe to normal cells).
------
Cancer Res. 2003 Aug 1;63(15):4375-83.
Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through
suppression of IkappaBalpha kinase and p65 phosphorylation: correlation with down-regulation of
cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1.
Shishodia S, Majumdar S, Banerjee S, Aggarwal BB. Cytokine Research Laboratory, Department of
Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard,
Houston, TX 77030, USA.
The process of tumorigenesis requires cellular transformation, hyperproliferation, invasion,
angiogenesis, and metastasis. Several genes that mediate these processes are regulated by the
transcription factor nuclear factor-kappaB (NF-kappaB). The latter is activated by various
carcinogens, inflammatory agents, and tumor promoters. Thus, agents that can suppress NF-kappaB
activation have the potential to suppress carcinogenesis. Ursolic acid, a pentacyclic triterpene
acid, has been shown to suppress the expression of several genes associated with tumorigenesis, but
whether ursolic acid mediates its effects through suppression of NF-kappaB is not understood. In the
study described in the present report, we found that ursolic acid suppressed NF-kappaB activation
induced by various carcinogens including tumor necrosis factor (TNF), phorbol ester, okadaic acid,
H(2)O(2), and cigarette smoke. These effects were not cell type specific. Ursolic acid inhibited DNA
binding of NF-kappaB consisting of p50 and p65. Ursolic acid inhibited IkappaBalpha
degradation, IkappaBalpha phosphorylation, IkappaBalpha kinase activation, p65
phosphorylation, p65 nuclear translocation, and NF-kappaB-dependent reporter gene
expression. Ursolic acid also inhibited NF-kappaB-dependent reporter gene expression
activated by TNF receptor, TNF receptor-associated death domain, TNF receptor-associated
factor, NF-kappaB-inducing kinase, IkappaBalpha kinase, and p65. The inhibition of NF-kappaB
activation correlated with suppression of NF-kappaB-dependent cyclin D1, cyclooxygenase 2,
and matrix metalloproteinase 9 expression. Thus, overall, our results indicate that ursolic
acid inhibits IkappaBalpha kinase and p65 phosphorylation, leading to the suppression of NF-
kappaB activation induced by various carcinogens. These actions of ursolic acid may mediate
its antitumorigenic and chemosensitizing effects.