Metformin and Aspirin: Anticancer Effects on A549 and Pc3 Cancer Cells and the Mechanisms of Action Publisher



Motafeghi F¹ ; Shahsavari R² ; Mortazavi P³ ; Babaei A² ; Samadimojaveri P⁴ ; Khojasteh OA⁵ ; Shokrzadeh M⁶ Show Affiliations
Source: Toxicology Research Published:2023

Abstract

Metformin exerts its anticancer effect through two mechanisms, directly affecting the tumor and indirectly reducing systemic insulin levels. The anticancer effects of aspirin occur by inhibiting Cyclooxygenase (COX)-2. COX-2 is absent in many cell types under normal conditions and increases under pathological conditions such as cancer. This study aims to investigate the effect of metformin and aspirin and their combination of them on A549 and PC3 cell lines. Metformin and aspirin were investigated separately and in combination on two cancer cell lines, A549 and PC3. The examined groups include the negative control of untreated cells and the positive control of cisplatin and drugs at concentrations of 15, 10, and 20 μg/ mL to investigate the mechanism of oxidative stress factors (reactive oxygen species, lipid peroxidation, Glutathione (GSH)) and apoptosis (lactate dehydrogenase). The results showed that aspirin, metformin, and their combination could affect cancer cell growth by damaging mitochondria, releasing reactive oxygen species, and activating the oxidative stress pathway. Also, these two drugs show the activation of the apoptotic pathway in cancer cells by increasing the lactate dehydrogenase factor and releasing it from the cells. By disrupting the balance of oxidants and antioxidants in the cell, metformin and aspirin cause an increase in the level of reactive oxygen species and a decrease in the level of glutathione reserves, followed by an increase in the level of lipid peroxidation and a decrease in cell viability. Unlike common chemotherapy drugs, these drugs have no known severe side effects; Therefore, in the not-so-distant future, these drugs can also be used as anticancer drugs. Highlights: Metformin and aspirin, commonly used drugs for diabetes and inflammation, inhibit the growth of cancer cell lines, A549 and PC3. Metformin and aspirin, either separately or in combination, can potentially impede cancer cell growth by disrupting mitochondrial function, inducing the release of reactive oxygen species (ROS), and activating oxidative stress pathways. Furthermore, these drugs can trigger apoptosis, a programmed cell death mechanism, in cancer cells by increasing lactate dehydrogenase (LDH) levels and facilitating its release from the cells. © 2023 The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.