Protein Information

ID 1221
Name peroxisome proliferator activated receptor gamma
Synonyms HUMPPARG; PAX8/PPARG fusion gene; NR1C3; PPAR gamma; PPAR gamma2; PPARG; PPARG 1; PPARG 2…

Compound Information

ID 477
Name biphenyl
CAS 1,1′-biphenyl

Reference

PubMed Abstract RScore(About this table)
19147759 Ichite N, Chougule MB, Jackson T, Fulzele SV, Safe S, Singh M: Enhancement of docetaxel anticancer activity by a novel diindolylmethane compound in human non-small cell lung cancer. Clin Cancer Res. 2009 Jan 15;15(2):543-52.
PURPOSE: This study was conducted to examine the cytotoxic effects of a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, 1,1-bis (3'-indolyl)-1-(p-biphenyl) methane (DIM-C-pPhC (6) H (5)), alone and in combination with docetaxel in vitro in A549 lung cancer cells and in vivo in nude mice bearing A549 orthotopic lung tumors. EXPERIMENTAL DESIGN: Isobolographic method was used to calculate combination index values from cell viability data. Apoptosis was evaluated in A549 cells by terminal deoxynucleotidyl transferase-mediated nick end labeling assay and measurement of cleaved poly (ADP-ribose) polymerase level. Expression of proteins was studied by Western blotting. A549 cells were implanted to induce orthotopic lung tumors in nude mice and the efficacy of docetaxel, DIM-C-pPhC (6) H (5), or combination was determined. Apoptosis and cleaved caspase-3 expression in the harvested tissues were studied by terminal deoxynucleotidyl transferase-mediated nick end labeling and immunohistochemistry, respectively. RESULTS: The combination index values (0.36-0.9) suggested synergistic to additive effects of docetaxel + DIM-C-pPhC (6) H (5) and resulted in the highest increase in percentage of apoptotic cells and expression of cleaved poly (ADP-ribose) polymerase, Bax, and N-cadherin compared with treatment with either agent. The combination also enhanced procaspase-3 and -9 cleavage. In vivo, docetaxel + DIM-C-pPhC (6) H (5) reduced lung weights by 57% compared with 39% by docetaxel or 22% by DIM-C-pPhC (6) H (5) alone, induced apoptosis in 43% of the tumor cells compared with 29% and 22% in tumors treated with docetaxel and DIM-C-pPhC (6) H (5), respectively, and increased procaspase-3 cleavage compared with either agent alone. CONCLUSIONS: These findings suggest potential benefit for use of docetaxel and DIM-C-pPhC (6) H (5) combination in lung cancer treatment.
81(1,1,1,1)