Andarine Plays a Robust In-vitro Anti-carcinogenic Role on A549 Cells Through Inhibition of Proliferation and Migration, and Activation of Cell-cycle Arrest, Senescence, and Apoptosis

Abstract Lung cancer is a highly aggressive malignancy with limited therapeutic options and a poor prognosis. Due to the development of resistance to chemotherapeutic drugs, novel therapeutic agents are required. Androgen receptor (AR) signaling affects various genes contributing to cancer characteristics, including cell cycle progression, proliferation, angiogenesis, and metastasis. The misregulation of AR signaling has been observed in many cancers, including lung cancer. Therefore, inhibiting AR signaling using anti-androgens, AR inhibitors, or AR-degrading molecules is a promising strategy for treating lung cancer. Selective androgen receptor modulators (SARMs) are small molecule drugs with a high affinity for the androgen receptor. Commonly used cell culture techniques (MTT assay, colony-formation assay, soft-agar assay, wound healing assay, EdU staining, Annexin-V/PI staining) were employed to investigate the potential anti-carcinogenic effect of andarine on A549 cells. The expression levels of several genes involved in the cell cycle and apoptosis processes were determined by qPCR. Our findings demonstrate that andarine inhibited growth, migration, and proliferation while inducing apoptosis in lung cancer cells. Gene expression analysis revealed that andarine significantly upregulated the expression of BAX, CDKN1A, PUMA , and GADD45A while downregulating MKI67, BIRC5 , and PCNA expression. Although there is no study on the utility of SARMs as inhibitors of lung cancer, we report the first study evaluating the potential anti-carcinogenic effects of andarine, a member of the SARMs, on lung cancer. Our results suggest that andarine could be considered as a promising drug candidate to test further for lung cancer treatment.