Antitumor Activity of a Polypyridyl Chelating Ligand: In Vitro and In Vivo Inhibition of Glioma

Abstract

Glioblastoma multiforme is an extremely aggressive and invasive form of central nervous system tumor commonly treated with the chemotherapeutic drug Temozolomide. Unfortunately, even with treatment, the median survival time is less than 12 months. 2,9-Di-sec-butyl-1,10-phenanthroline (SBP), a phenanthroline-based ligand originally developed to deliver gold-based anticancer drugs, has recently been shown to have significant antitumor activity in its own right. SBP is hypothesized to initiate tumor cell death via interaction with non-DNA targets, and considering most glioblastoma drugs kill tumors through DNA damage processes, SBP was tested as a potential novel drug candidate against glial-based tumors. In vitro studies demonstrated that SBP significantly inhibited the growth of rodent GL-26 and C6 glioma cells, as well as human U-87, and SW1088 glioblastomas/astrocytomas. Furthermore, using a syngeneic glioma model in mice, in vivo administration of SBP significantly reduced tumor volume and increased survival time. There was no significant toxicity toward nontumorigenic primary murine and human astrocytes in vitro, and limited toxicity was observed in ex vivo tissues obtained from noncancerous mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining and recovery assays suggest that SBP induces apoptosis in gliomas. This exploratory study suggests SBP is effective in slowing the growth of tumorigenic cells in the brain while exhibiting limited toxicity to normal cells and tissues and should therefore be further investigated for its potential in glioblastoma treatment.

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

“…We previously reported the antitumor effect of dsBPT on a glioblastoma cell line [16]. In the current study, we extended our investigation of this compound to HNSCC and lung cancer cells and provide the first data in regards to a combination therapy regime with this drug.…”

“…Therefore, the current study aimed to determine the anti-proliferative activity of 2,9-di- sec -butyl-1,10-phenanthroline (dsBPT). Augmenting our recent report in which this compound was tested for activity against glioblastoma tumor [16], the work reported here describes testing of this compound against head and neck and lung tumor cell lines and reports the first data in regard to a combined therapy regime with this agent providing new insight into the potential antitumor mechanism of dsBPT.…”

Kukoamine A inhibits human glioblastoma cell growth and migration through apoptosis induction and epithelial-mesenchymal transition attenuation

“…However, the distinct biological behavior of aggressive proliferation and invasive growth of GBM might be the unexplored therapeutic targets for treatment of this fatal tumor5. Thus, the discovery of new and specific chemotherapeutic agents inhibiting proliferation, migration and invasion of GBM cells are regarded as effective strategies to research and develop new drugs for GBM therapeutics101112131428.…”

“…Thus, inhibiting proliferation, migration and invasion of GBM cells are regarded as effective strategic modalities to screen a new drug for GBM treatment1011121314. Phytochemicals derived from medicinal herbs and dietary plants have recently received much attention as potential therapeutic and preventive agents for cancers, including GBM1516.…”