Saeed Mahdianipur, Saeed Mohammadi, Afifeh Jaefari, Homa Davoodi,
Volume 12, Issue 1 (10-2024)
Abstract
Background: Serotonin is a neurotransmitter with extensive physiological effects on the Central Nervous System (CNS) and various biological functions, including the regulation of immunity through 5-hydroxytryptamine receptors (5-HTRs) expressed by immune cells such as macrophages. Phenelzine, a medication used in managing treatment-resistant depression, acts as a potent monoamine oxidase inhibitor (MAOI). This enzyme metabolizes serotonin into 5-hydroxyindoleacetic acid (5-HIAA). Antidepressants e.g., Phenelzine may benefit patients with neurological disorders, who can also be prone to immune-related conditions and cancer. This study aimed to investigate the cytotoxic effects of Phenelzine, serotonin, and 5-HIAA on RAW264.7 macrophages.
Methods: We cultured RAW264.7 macrophages as a model that could express transporter receptors and enzymes associated with serotonin. We utilized MTT assay to evaluate the survival of RAW264.7 cells exposed to different concentrations of Phenelzine, serotonin, and 5-HIAA, pre-treated with lipopolysaccharide (LPS).
Results: Our findings revealed that LPS-treated RAW264.7 cells exhibited increased resistance to the cytotoxic effects of Phenelzine. Treatment with serotonin resulted in a concentration-dependent increase in RAW264.7 cell proliferation. In contrast, 5-HIAA did not significantly impact cell viability.
Conclusion: The present study reveals the effect of Phenelzine and serotonin on viability of RAW264.7 macrophages, particularly in the context of inflammation. It demonstrates increased resistance to the cytotoxic effects of Phenelzine in RAW264.7 cells treated with LPS. Our study contributes to a broader understanding of the potential systemic impacts of antidepressant medications and the intricate interplay between the serotonergic system and immune responses.
Saeed Mahdianipur , Mahafarin Maralani , Homa Davoodi ,
Volume 12, Issue 2 (10-2024)
Abstract
Monoamine neurotransmitters, including serotonin, dopamine, histamine, and adrenaline/noradrenaline (epinephrine/norepinephrine), are key neuromodulators in the nervous system that influence complex behavioral and cognitive functions. They also affect peripheral tissues and inflammation, playing a crucial role in the biology of various malignancies, including breast cancer, the most common cancer among women worldwide. These neurotransmitters are essential for mammary gland development and are linked to depression, a major breast cancer risk factor. Elevated levels of circulating proinflammatory cytokines in depression may mediate neuroendocrine, neural, and immune pathways, affecting the metabolism of monoamine neurotransmitters. In the tumor microenvironment, serotonin and norepinephrine generally exhibit pro-tumorigenic effects, while dopamine has shown promising anti-tumor activity by enhancing immune responses. Histamine also shows potential in anti-tumor immunity, although its effects on breast cancer progression remain inconclusive. Research into the relationship between these neurotransmitters and breast cancer cell growth highlights their significant role in breast cancer biology and their potential in improving treatment outcomes. This review explores the role of monoamine neurotransmitters in breast cancer progression, their immunomodulatory functions, and the therapeutic potential of targeting these neurotransmitters. By analyzing these complex relationships, we aim to illuminate novel therapeutic strategies that could enhance the clinical management of breast cancer.
