Angiogenesis plays a pivotal role in tumor growth and represents a key target for chemopreventive intervention. On the basis of the structural features and lack of target organ specificity of the synthetic dithiolethione oltipraz, inhibition of angiogenesis was assessed as a potential mechanism for its broad-based chemopreventive activity. The effects of oltipraz on the development and maturati...

Hypoxia-inducible factor-1alpha (HIF-1alpha) induces tumor proliferation, angiogenesis and metastasis. Reactive oxygen species, hypoxia, and growth factor stimulation induce HIF-1alpha, and the augmented HIF-1alpha activity confers upon cancer cells the ability to adapt to microenvironments. Oltipraz is a cancer chemopreventive agent and has an inhibitory effect on angiogenesis and tumor growth...

l,2-Dithiol-3-thiones, reported constituents of cruciferous vegetables, are five-membered cyclic sulfur-containing compounds with antioxidant, chemotherapeutic, and chemoprotective activities. The effects of dietary administration of a substituted l,2-dithiol-3-thione, oltipraz |5-( 2-pyrazinyl)-4-inethyl-l,2-dithiol-3-thione|, a potent antischistosomal agent, on »fiatimi! BI (AFBi) metabolism...

4-Methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz), a prototype drug candidate containing a 1,2-dithiole-3-thione moiety, has been widely studied as a cancer chemopreventive agent. Oltipraz and other novel 1,2-dithiole-3-thione congeners have the capability to prevent insulin resistance via AMP-activated protein kinase (AMPK) activation. Arachidonic acid (AA, a proinflammatory fatty acid...

The induction of phase 2 detoxifying enzymes, such as UDP-glucuronosyltransferases (UGTs), in response to an array of naturally occurring and synthetic agents, such as oltipraz (4-methyl-5-[2-pyrazinyl]-1,2-dithiole-3-thione), provides an effective means of protection against a variety of carcinogens. Transcription factor Nrf2 is an essential regulator of the inducible expression of detoxifying...

This study explored the efficacy of oltipraz, a dithiolthione to prevent lung cancer by delivering it directly to the lung as inhaled particulates to obtain maximum efficacy with no toxicity. Two exposure regimens were used to compare the efficacies of early (Regimen-A) versus late (Regimen-B) intervention in prevention of lung tumorigenesis in A/J mice. Female A/J mice were exposed to 10, 30 a...

BACKGROUND Cancer chemopreventive agents transcriptionally induce genes whose protein products can protect cells from chemical-induced carcinogenesis. Oltipraz, a dithiolthione, exerts chemopreventive responses through glutathione S-transferase (GST) induction. We investigated the role of the CCAAT/enhancer binding protein (C/EBP) in the induction of the GSTA2 gene (alpha class) by oltipraz and...

One of the major mechanisms of chemical protection against carcinogenesis, mutagenesis, and other forms of toxicity mediated by electrophiles is the induction of enzymes involved in their metabolism, particularly phase 2 enzymes such as glutathione S-transferases (GSTs), uridine diphosphate-glucuronosyltransferases, and NAD(P)H:quinone reductase. Furthermore, induction of phase 2 enzymes appear...

The chemoprevention agent oltipraz, one of the most active chemopreventive compounds in preclinical studies, has been shown to induce glutathione-S-transferase (GST) activity in animals. Oltipraz was evaluated in a Phase I trial at daily oral doses of 20 mg (L1), 50 mg (L2), and 100 mg (L3) and twice weekly doses of 125 mg (L4) taken for 6 months with 6 patients entered at L1 and L2 and 7 patie...

The induction of phase 2 detoxifying enzymes, such as UDP-glucuronosyltransferases (UGTs), in response to an array of naturally occurring and synthetic agents, such as oltipraz (4-methyl-5-[2-pyrazinyl]-1,2-dithiole-3thione), provides an effective means of protection against a variety of carcinogens. Transcription factor Nrf2 is an essential regulator of the inducible expression of detoxifying ...