Abstract 2386: Investigating cyclopamine tartrate as a potential suppressor of lung adenocarcinoma and squamous cell carcinoma

Abstract

Abstract Lung cancer is the leading cause of death by cancer, and non-small cell lung cancer comprises of 85-90% of lung cancer cases. Previous studies have demonstrated the importance of heme in mitochondrial metabolism and OXPHOS. Heme is an essential molecule in the oxidative phosphorylation pathway especially since Complex II-IV all contain heme. During lung tumorigenesis there is a marked increase in heme synthesis and uptake; other protein and enzymes relating to heme were also upregulated. Heme-sequestration proteins (HeSPs) have shown high effectiveness in suppressing the development and progression of lung adenocarcinoma and squamous cell carcinoma, therefore targeting heme using CycT should yield similar results. Previous studies have indicated that cyclopamine tartrate (CycT) can effectively arrest lung tumor growth and progression. CycT does this by inhibiting the levels of proteins and enzymes involved in heme uptake, synthesis, as well as reducing heme synthesis and degradation in adenocarcinoma. We therefore aim to examine the effectiveness of CycT in both, adenocarcinoma and squamous cell carcinoma.In vitro experiments using NSCLC adenocarcinoma cell line A549 and squamous cell carcinoma HCC15 are in progression with initial results supporting the hypothesis. Cell proliferation assays have shown a marked decrease in CycT-treated groups in both cell lines. Based on colony formation assays, results indicate that CycT inhibits colony formation. Heme synthesis and degradation have also shown the effectiveness of CycT in suppressing tumorigenesis in both cell types. Oxygen consumption rates of both cell types were examined with CycT inhibiting oxygen consumption. Overall, in vitro experiments support the idea that CycT can suppress or arrest lung adenocarcinoma and squamous cell carcinoma. Citation Format: Eranda Berisha, Adnin Ashrafi, Maria Del Carmen Chacon Castro, Li Zhang. Investigating cyclopamine tartrate as a potential suppressor of lung adenocarcinoma and squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2386.