Novel Colchicine-Binding Site Inhibitor Shows Anti-Cancer Efficacy Against Oral Cancer

Objectives: To investigate the anti-cancer potential of a novel colchicine-binding site inhibitor (CBSI), SP-1-39, as an alternative treatment for head and neck cancer (HNC) using in vitro cell culture techniques and in vivo tumor studies.
Methods: A comprehensive characterization of SP-1-39 was conducted in HNC cell lines, A-253 and Detroit 562 in various in vitro assays including cell proliferation, colony formation, and cell migration. Western blotting was used to evaluate the induction of apoptosis of SP-1-39 in HNC cell lines in a dose-dependent manner. A subcutaneous Detroit 562 xenograft mouse model was used to study the in vivo tumor suppression. Mice were divided into two treatment groups: (1) Control (5% DMSO, 35% PEG300, 60% saline, intravenous injection, two times per week) or (2) SP-1-39 (2.5mg/kg, 5% DMSO, 35% PEG300, 60% saline, intravenous injection, two times per week).
Results: We report evidence of SP-1-39’s robust anti-cancer activity in two HNC cell lines, A-253 and Detroit 562. SP-1-39 exhibits potent inhibition of proliferation in both cell lines, maintaining a low IC₅₀ value ranging from 0.56 to 1.8nM. Moreover, it effectively suppresses colony formation, impedes cell migration in a Transwell migration assay, and induces apoptosis in a dose-dependent manner. In a subcutaneous Detroit 562 xenograft mouse model, treatment with 2.5mg/kg SP-1-39 via intravenous injection twice weekly resulted in an 84.3% reduction in final tumor volume, with no observed loss in body weight. Results were evaluated using two-way ANOVA with Dunnett tests (α=0.05).
Conclusions: SP-1-39 displays strong anti-cancer activity in HNC cell lines in a variety of in vitro cell culture assays. SP-1-39 efficiently suppressed tumor growth in a subcutaneous xenograft mouse model with limited to no toxicity in the mice. Together, these results show SP-1-39 is a promising candidate for further evaluation in HNC treatment.