Monoamine Oxidase (MAO) as a Potential Target for Anticancer Drug Design and Development.

Monoamine oxidases (MAOs) are oxidative enzymes that catalyze the conversion of biogenic amines into their corresponding aldehydes and ketones through oxidative deamination. Owing to the crucial role of MAOs in maintaining functional levels of neurotransmitters, the implications of its distorted activity have been associated with numerous neurological diseases. Recently, an unanticipated role of MAOs in tumor progression and metastasis has been reported. The chemical inhibition of MAOs might be a valuable therapeutic approach for cancer treatment. In this review, we reported computational approaches exploited in the design and development of selective MAO inhibitors accompanied by their biological activities. Additionally, we generated a pharmacophore model for MAO-A active inhibitors to identify the structural motifs to invoke an activity.

Selective Estrogen Receptor Modulators (SERMs) Synergize with Cisplatin, Induce Apoptosis and Suppress Cellular Migration and Colony Formation of Lung Cancer Cells.

BACKGROUND: Lung cancer remains the leading cause of cancer-related deaths worldwide. Hence, novel therapeutic approaches targeting crucial pathways are needed to improve its treatment. Previous studies have verified the involvement of the estrogen pathway, mediated through estrogen receptor ß (ERß), in the development and progression of lung carcinogenesis. Selective estrogen receptor modulators (SERMs) are a group of estrogen receptor agonists/antagonists that have tissue selective effects. Many of the available SERMs are used for the management of breast cancer. However, their role in lung cancer is still under investigation. OBJECTIVES: The aim of this research is to investigate the anti-tumorigenic activity of the selective estrogen receptor modulators, tamoxifen, raloxifene, and toremifene, against different lung cancer cell lines. METHODS: The anti-proliferative and combined effects of SERMs with standard chemotherapy were evaluated by MTT assay. Cell migration was assessed using a wound-healing assay. The mechanism of cell death was determined using the Annexin V-FITC/ propidium iodide staining flow cytometry method. Cells' capability to form colonies was evaluated by soft agar colony formation assay. Estrogen receptors expression was determined using real-time PCR. RESULTS: Our results have demonstrated the presence of ERß in A549, H1299, and H661 lung cancer cells. Cellular proliferation assay suggested that SERMs have significantly reduced lung cancer cells proliferation in a time and concentration- dependent manner. Additionally, SERMs exhibited a synergistic effect against A549 cells when combined with cisplatin. SERMs treatment have increased cell apoptosis and resulted in concentration-dependent inhibition of cell migration and colony formation of A549 cells. CONCLUSION: Selective estrogen receptor modulators may possess potential therapeutic utility for the treatment of lung cancer as monotherapy or in combination with standard chemotherapy.