A potent indole-3-carbinol derived antitumor agent with pleiotropic effects on multiple signaling pathways in prostate cancer cells.

doi:10.1158/0008-5472.CAN-07-0794

Paper

A potent indole-3-carbinol derived antitumor agent with pleiotropic effects on multiple signaling pathways in prostate cancer cells.

Published Aug 15, 2007 · J. Weng, Chen-Hsun Tsai, S. Kulp

Cancer research

Q1 SJR score

71

Citations

1

Influential Citations

Full textSemantic Scholar

Abstract

Indole-3-carbinol has emerged as a promising chemopreventive agent due to its in vivo efficacy in various animal models. However, indole-3-carbinol exhibits weak antiproliferative potency and is unstable in acidic milieu. Thus, this study was aimed at exploiting indole-3-carbinol to develop potent antitumor agents with improved chemical stability. This effort culminated in OSU-A9 {[1-(4-chloro-3-nitrobenzenesulfonyl)-1H-indol-3-yl]-methanol}, which is resistant to acid-catalyzed condensation, and exhibits 100-fold higher apoptosis-inducing activity than the parent compound. Relative to indole-3-carbinol, OSU-A9 displays a striking qualitative similarity in its effects on the phosphorylation or expression of multiple signaling targets, including Akt, mitogen-activated protein kinases, Bcl-2 family members, survivin, nuclear factor-kappaB, cyclin D1, p21, and p27. The ability of OSU-A9 to concurrently modulate this broad range of signaling targets underscores its in vitro and in vivo efficacy in prostate cancer cells. Nevertheless, despite this complex mode of mechanism, normal prostate epithelial cells were less susceptible to the antiproliferative effect of OSU-A9 than PC-3 and LNCaP prostate cancer cells. Treatment of athymic nude mice bearing established s.c. PC-3 xenograft tumors with OSU-A9 at 10 and 25 mg/kg i.p. for 42 days resulted in a 65% and 85%, respectively, suppression of tumor growth. Western blot analysis of representative biomarkers in tumor lysates revealed significant reductions in the intratumoral levels of phosphorylated (p-) Akt, Bcl-xL, and RelA, accompanied by robust increases in p-p38 levels. In conclusion, the ability of OSU-A9 to target multiple aspects of cancer cell survival with high potency suggests its clinical value in prostate cancer therapy.

Non-RCT

Animal Study

Highly Cited

Study Snapshot

OSU-A9, a potent indole-3-carbinol derivative with improved stability, effectively suppresses prostate cancer growth by targeting multiple cancer cell survival pathways.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

A potent indole-3-carbinol derived antitumor agent with pleiotropic effects on multiple signaling pathways in prostate cancer cells.

Sign up to use Study Snapshot

References

Single-Dose and Multiple-Dose Administration of Indole-3-Carbinol to Women: Pharmacokinetics Based on 3,3′-Diindolylmethane

Indole-3-carbinol (I3C) shows pharmacokinetic similarities across different doses, with 3,3′-diindolylmethane (DIM) levels near or below 15 ng/mL by 24 hours in women.

Peroxisome Proliferator-Activated Receptor γ-Independent Repression of Prostate-Specific Antigen Expression by Thiazolidinediones in Prostate Cancer Cells

Thiazolidinediones suppress prostate-specific antigen (PSA) secretion independently of PPAR activation, offering potential for designing AR-ablative agents.

The natural chemopreventive compound indole-3-carbinol: state of the science.

Indole-3-carbinol (I3C) has potential anticancer effects by modulating nuclear transcription factors, enhancing DNA repair, and promoting carcinogen metabolism, but its potential for promoting cancer has not been proven.

Inhibition of Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Is Not Sufficient to Account for Indole-3-Carbinol–Induced Apoptosis in Some Breast and Prostate Tumor Cells

Indole-3-carbinol's apoptosis induction in breast and prostate tumor cells is not directly correlated with inhibition of PI3K/PKB signaling.

Synthesis and biological activities of novel aryl indole-2-carboxylic acid analogs as PPARgamma partial agonists.

Novel aryl indole-2-carboxylic acid analogs show potential as selective PPAR modulators, reducing hyperglycemia in a type 2 diabetes mouse model with comparable plasma exposure to rosiglitazone.

Citations

Comparative safety, pharmacokinetics, and off-target assessment of 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane in mouse and dog: implications for therapeutic development.

Low doses of C-DIM12 do not induce pathology and can modulate targets relevant to neurodegeneration and cancer, making it a potential therapeutic platform.

Cruciferous vegetable-derived indole-3-carbinol prevents coronavirus cell egression mechanisms in tracheal and intestinal 3D in vitro models.

Indole-3-carbinol, found in Cruciferous vegetables, shows potential in preventing coronavirus cell egression processes, potentially reducing the clinical severity of future pandemics.

Anti Cancer Activity of Naturally Occurring Heterocyclic Compound

Indole compounds found in cruciferous vegetables show powerful anti-cancer capabilities by blocking angiogenesis, overcoming drug resistance, invasion, and changing the epithelial-to-mesenchymal transition phenotype.

Identification of the HECT domain binding of indole-3-carbinol (I3C) derivatives for breast cancer therapy

Compound A3, a HECT domain binding inhibitor based on indole-3-carbinol (I3C), shows potential as a breast cancer therapy by inhibiting proliferation, invasion, and induced apoptosis in MDA-MB-231 cells.

Natural products targeting cancer stem cells: Implications for cancer chemoprevention and therapeutics.

Targeting cancer stem cells with natural products may be a novel strategy for cancer chemoprevention and therapeutics, as they have minimal toxicity compared to traditional cancer therapy drugs.

The Role of Phytochemicals in Cancer Prevention and Cure

Phytochemicals from medicinal plants play a crucial role in cancer prevention and cure through antioxidant, pro-oxidant, apoptosis, necrosis, autophagy, and miRNA regulation.

An Update on the Role of Dietary Phytochemicals in Human Skin Cancer: New Insights into Molecular Mechanisms

Dietary phytochemicals found in whole fruits and vegetables show potential in preventing skin cancer by acting as anti-inflammatory, antioxidant, and anti-angiogenic agents.

[1-(4-chloro-3-nitrobenzenesulfonyl)-1H-indol-3-yl]-methanol, an indole-3-carbinol derivative, inhibits glutamate release in rat cerebrocortical nerve terminals by suppressing the P/Q-type Ca2+ channels and Ca2+/calmodulin/protein kinase A pathway

CIM, an indole-3-carbinol derivative, inhibits glutamate release in rat cerebrocortical nerve terminals by suppressing P/Q-type calcium channels and the Ca2+/calmodulin/AC/PKA pathway.