Investigation of anti-cancer effect of 3α-acetoxy-25-hydroxy-olean-12-en-28-oic acid in squamous cell lung cancer

Squamous cell lung carcinoma is a histological subtype of non-small cell lung cancer and is one of the leading causes of cancer-related mortality due to its high mutation frequency and limited treatment options. Therefore, studies aiming to develop more effective antineoplastic agents with reduced cytotoxicity for healthy cells are of great importance. 3a-Acetoxy-25-hydroxy-olean-12-en-28-oic acid is a derivative of oleanolic acid. Some derivatives of oleanolic acid are currently under investigation and have been included in clinical trials as potential drug candidates. In this study, we aimed to demonstrate that 3a-Acetoxy-25-hydroxy-olean-12-en-28-oic acid, which has unknown effects on cancer cells and limited information in the literature, may have anticancer effects. In our study, the cytotoxic, apoptotic, migratory, and anchorage-independent colony-forming effects of 3a-Acetoxy-25-hydroxy-olean-12-en-28-oic acid were investigated using cell culture experiments on squamous cell lung cancer cell lines; SK-MES-1, H520 and a healthy lung bronchial epithelial cell line BEAS-2B. The molecular mechanisms of 3a-Acetoxy-25-hydroxy-olean-12-en-28-oic acid treatment in cells were investigated by RNA sequence and bioinformatic analyses, RT-PCR and Western Blot methods. Our findings demonstrated that 3a-Acetoxy-25-hydroxy-olean-12-en-28-oic acid suppressed cell proliferation, migration, and anchorage-independent colony formation in squamous cell lung cancer cell lines. Additionally, it activated the endoplasmic reticulum stress pathway, thereby inducing apoptosis. Our findings provided important contributions to the limited knowledge of 3a-Acetoxy-25-hydroxy-olean-12-en-28-oic acid in the literature. In conclusion, the molecule may be a potential antineoplastic agent open to development against squamous cell lung cancer and its molecular effects should be investigated in more detail in future studies.