Document Detail

Inhalation delivery of a novel diindolylmethane derivative for the treatment of lung cancer.
MedLine Citation:
PMID:  20978159     Owner:  NLM     Status:  MEDLINE    
The purpose of this study was to determine the anticancer efficacy of 1,1-bis (3'-indolyl)-1-(p-biphenyl) methane (DIM-C-pPhC₆H₅) by inhalation delivery alone and in combination with i.v. docetaxel in a murine model for lung cancer. An aqueous DIM-C-pPhC₆H₅ formulation was characterized for its aerodynamic properties. Tumor-bearing athymic nude mice were exposed to nebulized DIM-C-pPhC₆H₅, docetaxel, or combination (DIM-C-pPhC₆H₅ plus docetaxel) using a nose-only exposure technique. The aerodynamic properties included mass median aerodynamic diameter of 1.8 ± 0.3 μm and geometric SD of 2.31 ± 0.02. Lung weight reduction in mice treated with the drug combination was 64% compared with 40% and 47% in mice treated with DIM-C-pPhC₆H₅ aerosol and docetaxel alone, respectively. Combination treatment decreased expression of Akt, cyclin D1, survivin, Mcl-1, NF-κB, IκBα, phospho-IκBα, and vascular endothelial growth factor (VEGF) and increased expression of c-Jun NH₂-terminal kinase 2 and Bad compared with tumors collected from single-agent treatment and control groups. DNA fragmentation was also enhanced in mice treated with the drug combination compared with docetaxel or DIM-C-pPhC₆H₅ alone. Combination treatment decreased expressions of VEGF and CD31 compared with single-agent treated and control groups. These results suggest that DIM-C-pPhC₆H₅ aerosol enhanced the anticancer activity of docetaxel in a lung cancer model by activating multiple signaling pathways. The study provides evidence that DIM-C-pPhC₆H₅ can be used alone or in combination with other drugs for the treatment of lung cancer using the inhalation delivery approach.
Nkechi Ichite; Mahavir Chougule; Apurva R Patel; Tanise Jackson; Stephen Safe; Mandip Singh
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-26
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  9     ISSN:  1538-8514     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-11     Completed Date:  2011-02-28     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3003-14     Citation Subset:  IM    
Copyright Information:
©2010 AACR.
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
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MeSH Terms
Administration, Inhalation
Antineoplastic Agents / administration & dosage,  adverse effects
Carcinoma, Non-Small-Cell Lung / drug therapy*,  pathology
Cell Line, Tumor
Drug Delivery Systems
Indoles / administration & dosage*,  adverse effects,  chemistry
Lung Neoplasms / drug therapy*,  pathology
Mice, Nude
Models, Biological
Nasal Sprays
Xenograft Model Antitumor Assays
Grant Support
Reg. No./Substance:
0/1,1-bis(3'-indolyl)-1-(4-biphenyl)methane; 0/Antineoplastic Agents; 0/Indoles; 0/Nasal Sprays; 0/diindolylmethane

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