1,1-Bis (3′-indolyl)-1-(p-substitutedphenyl)methane compounds inhibit lung cancer cell and tumor growth in a metastasis model

1,1-Bis(3-indolyl)-1-(p-substitutedphenyl)methane (C-DIM) compounds exhibit remarkable antitumor activity with low toxicity in various cancer cells including lung tumors. Two C-DIM analogs, DIM-C-pPhOCH3 (C-DIM-5) and DIM-C-pPhOH (C-DIM-8) while acting differentially on the orphan nuclear receptor,...

Full description

Saved in:
Bibliographic Details
Published in:European journal of pharmaceutical sciences 2013-10, Vol.50 (2), p.227-241
Main Authors: Andey, Terrick, Patel, Apurva, Jackson, Tanise, Safe, Stephen, Singh, Mandip
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Anisoles - administration & dosage
Antineoplastic Agents - administration & dosage
Caco-2 Cells
Cell Line, Tumor
Cell Survival - drug effects
Female
Humans
Indoles - administration & dosage
Inhalation
Lung - metabolism
Lung - pathology
Lung Neoplasms - drug therapy
Lung Neoplasms - metabolism
Lung Neoplasms - secondary
Metastatic
Mice
Mice, Nude
Nebulizer
Nuclear Receptor Subfamily 4, Group A, Member 1 - metabolism
Nur77/TR3
Permeability
Phenols - administration & dosage
Taxoids - administration & dosage
Tumor Burden - drug effects
Vascular Endothelial Growth Factor A - metabolism
Xenograft Model Antitumor Assays
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:1,1-Bis(3-indolyl)-1-(p-substitutedphenyl)methane (C-DIM) compounds exhibit remarkable antitumor activity with low toxicity in various cancer cells including lung tumors. Two C-DIM analogs, DIM-C-pPhOCH3 (C-DIM-5) and DIM-C-pPhOH (C-DIM-8) while acting differentially on the orphan nuclear receptor, TR3/Nur77 inhibited cell cycle progression from G0/G1 to S-phase and induced apoptosis in A549 cells. Combinations of docetaxel (doc) with C-DIM-5 or C-DIM-8 showed synergistic anticancer activity in vitro and these results were consistent with their enhanced antitumor activities invivo. Respirable aqueous formulations of C-DIM-5 (mass median aerodynamic diameter of 1.92±0.22μm and geometric standard deviation of 2.31±0.12) and C-DIM-8 (mass median aerodynamic diameter of 1.84±0.31μm and geometric standard deviation of 2.11±0.15) were successfully delivered by inhalation to athymic nude mice bearing A549 cells as metastatic tumors. This resulted in significant (p
ISSN:0928-0987
1879-0720
DOI:10.1016/j.ejps.2013.07.007