Antitumor Activity of 2,9-Di-Sec-Butyl-1,10-Phenanthroline

Abstract

The anti-tumor effect of a chelating phen-based ligand 2,9-di-sec-butyl-1,10-phenanthroline (dsBPT) and its combination with cisplatin were examined in both lung and head and neck cancer cell lines and xenograft animal models in this study. The effects of this agent on cell cycle and apoptosis were investigated. Protein markers relevant to these mechanisms were also assessed. We found that the inhibitory effect of dsBPT on lung and head and neck cancer cell growth (IC50 ranged between 0.1–0.2 μM) was 10 times greater than that on normal epithelial cells. dsBPT alone induced autophagy, G1 cell cycle arrest, and apoptosis. Our in vivo studies indicated that dsBPT inhibited tumor growth in a dose-dependent manner in a head and neck cancer xenograft mouse model. The combination of dsBPT with cisplatin synergistically inhibited cancer cell growth with a combination index of 0.3. Moreover, the combination significantly reduced tumor volume as compared with the untreated control (p = 0.0017) in a head and neck cancer xenograft model. No organ related toxicities were observed in treated animals. Our data suggest that dsBPT is a novel and potent antitumor drug that warrants further preclinical and clinical development either as a single agent or in combination with known chemotherapy drugs such as cisplatin.

β-Cyclodextrin complex improves the bioavailability and antitumor potential of cirsiliol, a flavone isolated from Leonotis nepetifolia (Lamiaceae)

“…Although the selectivity index values for positive control doxorubicin have been more expressive that found for CD-CIR inclusion complexes, studies have shown that many tumors have acquired resistant to treatment with this drug. In addition, conventional drugs used in chemotherapy present various side effects as mutagenicity, teratogenicity, nephrotoxicity, neuropathy, myelosuppression, immunosuppression and cardiotoxicity [3, 4, 30]. Thus, the results obtained for the inclusion complex encouraged us to determine the activity against S-180 murine cell line in vitro and in vivo .…”