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Acetylsalicylic acid and salicylic acid present anticancer properties against melanoma by promoting nitric oxide-dependent endoplasmic reticulum stress and apoptosis
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Acetylsalicylic acid and salicylic acid present anticancer properties against melanoma by promoting nitric oxide-dependent endoplasmic reticulum stress and apoptosis
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Acetylsalicylic acid and salicylic acid present anticancer properties against melanoma by promoting nitric oxide-dependent endoplasmic reticulum stress and apoptosis
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Journal Article
Acetylsalicylic acid and salicylic acid present anticancer properties against melanoma by promoting nitric oxide-dependent endoplasmic reticulum stress and apoptosis
2020
Overview
Melanoma is the most aggressive and fatal type of skin cancer due to being highly proliferative. Acetylsalicylic acid (ASA; Aspirin) and salicylic acid (SA) are ancient drugs with multiple applications in medicine. Here, we showed that ASA and SA present anticancer effects against a murine model of implanted melanoma. These effects were also validated in 3D- and 2D-cultured melanoma B16F10 cells, where the drugs promoted pro-apoptotic effects. In both in vivo and in vitro models, SA and ASA triggered endoplasmic reticulum (ER) stress, which culminates with the upregulation of the pro-apoptotic transcription factor C/EBP homologous protein (CHOP). These effects are initiated by ASA/SA-triggered Akt/mTOR/AMPK-dependent activation of nitric oxide synthase 3 (eNOS), which increases nitric oxide and reactive oxygen species production inducing ER stress response. In the end, we propose that ASA and SA instigate anticancer effects by a novel mechanism, the activation of ER stress.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Acids
/ AMP-Activated Protein Kinases - metabolism
/ Animals
/ Aspirin
/ CCAAT/enhancer-binding protein
/ Endoplasmic Reticulum Stress - drug effects
/ Humanities and Social Sciences
/ Male
/ Melanoma
/ Nitric Oxide Synthase Type III - metabolism
/ Proto-Oncogene Proteins c-akt - metabolism
/ Salicylic Acid - pharmacology
/ Salicylic Acid - therapeutic use
/ Science
/ Skin Neoplasms - drug therapy
