Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Intracellular ROS Generation Mediates Maleimide-induced Cytotoxicity in Leukemia Cells

Author(s): Daiane Rosolen, Vania F. Noldin, Evelyn Winter, Fabiola B. Filippin-Monteiro, Fatima Campos-Buzzi, Valdir Cechinel-Filho and Tania B. Creczynski-Pasa

Volume 15, Issue 9, 2015

Page: [1164 - 1173] Pages: 10

DOI: 10.2174/1871520615666150629102158

Price: $65


Maleimides consist of an important class of compounds easily synthesized with multiple functional group modification that provides expressive pharmacological properties including, antitumoral activity, mediated mainly by oxidative stress. For this reason, the present study was designed to evaluate the cytotoxicity and the role of reactive oxygen species (ROS) in maleimide-induced cell death. Cell viability assays were performed to determine the cell death type in leukemia cell line induced by the compounds. The oxidative stress in maleimidetreated cells was characterized by antioxidant enzymes activities, intracellular ROS generation, and lipid peroxidation. In addition, we evaluated mitochondrial membrane potential and ATP level. Maleimide derivatives exhibited cytotoxic effects in leukemia cells with significantly increased ROS generation. However, cell viability was partly restored by catalase-treated cells. Caspases activities and caspase-independent key genes related to apoptosis were not altered by maleimides, suggesting necrosis as the main cell death process. Maleimide-induced necrosis was associated with oxidative stress, as an imbalance between ROS levels and glutathione reductase (GR) activity. This damage was also demonstrated by loss of mitochondrial membrane potential (MMP) and ATP depletion in cells treated with maleimide derivatives. These findings strongly confirmed that maleimide derivatives promoted cell death in leukemia cells triggered by oxidative stress, indicating that these compounds might be promising antitumor agents or lead molecules.

Keywords: Cytotocixity, leukemia, maleimides, mitochondrial membrane potential, necrosis, ROS generation.

Graphical Abstract

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy