Effects of Arsenic on the macrophages in colorectal malignancy
Effects of Arsenic on the macrophages in colorectal malignancy
Fatemeh Maghool,1,*Mohammad Hassan Emami,2Samane Mohammadzadeh,3Safoora Mohammadzadeh,4
1. Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran 2. Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran 3. Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran 4. Poursina Hakim Digestive Diseases Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
Introduction: Cancer, as the most common leading cause of death, results from interactions between carcinogens and immune/non-immune cells. Macrophages are the professional phagocytes which help to recognizing the transformed cells and removing the immune-gene cancerous cells. Arsenic, as a chemical carcinogen, could result in the risk of cancer progression through induction of proliferation and apoptosis via activation of phosphatidylinositol 3‑kinase (PI3K) /protein kinase B (AKT) signaling pathway. This review discusses role of arsenic on PI3K/AKT signaling pathway in the immune cells in colorectal cancer (CRC).
Methods: The English database were searched using the search terms "Arsenic", "macrophage", "PI3K/AKT signaling pathway", and "colorectal cancer" PI3K/AKT signaling pathway. Only published articles have been included.
Results: According to various studies, arsenic has powerful immune-toxic effects on immune cells, including macrophages. This heavy metal is capable to target the monocyte/macrophage by inhibiting differentiation, reducing endocytosis and phagocytosis activity, and inducing apoptosis. It could interfere with the antigen-presenting activity of macrophages. Arsenic induces immunosuppression that can lead to infectious diseases and cancers. Multiple molecular and cellular mechanisms can mediate arsenic immune-toxicity, including reactive oxygen species (ROS) production, alteration of redox-sensitive signaling pathways, DNA damage, epigenetic effects, and inflammasome inhibition. Multiple signaling pathways such as the PI3K/AKT pathway play a major role in immune-toxicity of As. PI3K/AKT pathway is one of the signaling pathways which regulates cell proliferation, cell cycle and apoptosis. Over-activation of this pathway may lead to malignant tumors and cancer progression.
PI3Ks play role in phagosome formation, antigen-presenting and innate immune response. This pathway is normally activated by extracellular signals including growth factors, cytokines and hormones and regulates macrophages activities. However, PI3K/AKT pathway could be inhibited directly or indirectly (through As-induced ROS) by arsenic toxicity, and ultimately promoted macrophage autophagy and dysfunctionalities. Therefore, As could alter macrophages activities (cytokine production, phagocytosis and antigen presentation) through inhibition of PI3K/AKT pathway.
Conclusion: in conclusion, arsenic has an immunosuppressive effect on macrophages by inhibiting the PI3K/AKT pathway which can help to progression of tumors in colorectal cancer.