ArticleBreast cancer research : BCR2007
1,1-Bis(3'-indolyl)-1-(p-biphenyl)methane inhibits basal-like breast cancer growth in athymic nude mice.
Article in Breast cancer research : BCR, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 21 citations in OpenAlex.
- Comparative safety, pharmacokinetics, and off-target assessment of 1,1-bis(3'-indolyl)-1-(Toxicology research · 2024Article
- Stx2 Induces Differential Gene Expression and Disturbs Circadian Rhythm Genes in the Proximal Tubule.Toxins · 2022Article
- Evaluation of self-emulsified DIM-14 in dogs for oral bioavailability and in Nu/nu mice bearing stem cell lung tumor models for anticancer activity.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- A novel bisindole-PBD conjugate causes DNA damage induced apoptosis via inhibition of DNA repair pathway.Cancer biology & therapy · 2014Article
- EphA2 targeting pegylated nanocarrier drug delivery system for treatment of lung cancer.Pharmaceutical research · 2014Article
- Targeting NR4A1 (TR3) in cancer cells and tumors.Expert opinion on therapeutic targets · 2011Review
- A Role for the PPARgamma in Cancer Therapy.PPAR research · 2008Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introduction1,1-Bis (3'-indolyl)-1-(p-biphenyl) methane (CDIM9) has been identified as a new peroxisome proliferator-activated receptor (PPAR)-gamma agonist that exhibits both receptor dependent and independent antitumor activities. CDIM9 has not previously been studied with respect to its effects against basal-like breast cancer. Our goal in the present study was to investigate the anti-basal-like breast tumor activity of CDIM9 in vitro and in vivo.
methodsThe effects of CDIM9 on cell protein and DNA syntheses were determined in basal-like breast cancer MDA-MB231 and BT549 cells in vitro. Maximum tolerated dose and dose-limited toxicity were determined in BalB/c mice, and antitumor growth activities were assessed in MDA-MB231 basal-like breast tumor xenografts in athymic nude mice.
resultsCDIM9 exhibited selective cell cytotoxicity and anti-proliferation effects on basal-like breast cancer lines. In MDA-MB231 cell, CDIM9 induced caveolin-1 and p27 expression, which was significantly downregulated by co-treatment with the PPAR-gamma antagonist GW9662. Nonsteroidal anti-inflammatory drug-activated gene-1 and activating transcription factor-3 were upregulated by CDIM9 through a PPAR-gamma independent pathway. CDIM9 (40 mg/kg daily, intraperitoneally, for 35 days) inhibited the growth of subcutaneous MDA-MB231 tumor xenografts by 87%, and produced a corresponding decrease in proliferation index. Nearly half of the treated mice (46%) had complete durable remissions, confirmed by histology. The growth of an established tumor was inhibited by CDIM9 treatment (64 mg/kg daily, intraperitoneally, for 10 days), with a mean tumor growth inhibition of 67% as compared with controls. CDIM9 induced increases in tumor caveolin-1 and p27 in vivo, which may contribute to its antitumor activity in basal-like breast cancer.
conclusionCDIM9 showed potent antiproliferative effects on basal-like breast cancer cell in tissue culture and dramatic growth inhibition in animal models at safe doses. These findings justify further development of this drug for treatment of basal-like breast cancer.
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