Abstract 2328: Interrogating the anti-cancer effects of co-enzyme Q10 (CoQ10) identifies metabolic and mitochondrial apoptotic responses as primary mechanisms in squamous cell carcinoma model

Abstract

Targeting mitochondrial function as a therapeutic modality in cancer has been extensively investigated. BPM 31510 is a proprietary drug-lipid nanoconjugate formulation enabling delivery of supra-physiological concentrations of oxidized CoQ10 specifically into mitochondria. In this study, the anti-cancer properties of CoQ10 in squamous cell carcinoma (SCC) and its mechanism of action were investigated in in vivo xenograft and in vitro model systems. Nude mice were inoculated with a squamous carcinoma cell line isolated from tongue, SCC-25, and treated with a topical formulation containing 1.5% or 5% CoQ10. Treatment was associated with a dose-dependent delay in the detection of palatable tumors (14 ± 3 days vehicle control, 27 ± 7 days 1.5% cream, 39 ± 9 days 5% cream), (p<0.05). Histology and immunostaining analysis demonstrated a decrease in expression of VEGF in the treatment groups (p<0.05). The anti-cancer mechanism of action of CoQ10 was further investigated by interrogating the influence of CoQ10 exposure on molecular profiles using SCC-25 cells in vitro. Cell based assays, mRNA-based RT-PCR assays, and protein-based antibody chip microarrays confirmed an apoptotic response as a major anti-cancer effect in SCC-25 cells in response to CoQ10 exposure. The change in anti- and pro-apoptotic markers (Bcl-2 and caspase families) was independently confirmed by western blotting. In addition, global proteomic analysis revealed alterations in key metabolic proteins in the Pentose Phosphate Pathway (PPP). For example, expression of Transaldolase 1, an enzyme involved in the cellular protection against oxidative stress, resistance/susceptibility to apoptosis, and SCC tumor development and progression, was reduced 1.5 fold at both 6 and 24 hour time point in response to CoQ10 treatment. Together, the data suggests that CoQ10 influences cancer metabolism and redox pathway in activating apoptosis in SCC cancer model. Citation Format: Niven R. Narain, Shiva Kazerounian, Shivani Khatu, Anne R. Diers, John McCook, Stephane Gesta, Robert S. Kirsner, Brian Berman, Rangaprasad Sarangarajan. Interrogating the anti-cancer effects of co-enzyme Q10 (CoQ10) identifies metabolic and mitochondrial apoptotic responses as primary mechanisms in squamous cell carcinoma model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2328.