Anticancer Function and ROS-Mediated Multi-Targeting Anticancer Mechanisms of Copper (II) 2-hydroxy-1-naphthaldehyde...

Area of Science:

• Medicinal Chemistry
• Cancer Biology
• Molecular Pharmacology

Background:

• Targeting multiple oncoproteins with a single molecule offers a rational approach to cancer therapy.
• Novel copper (Cu2+) compounds derived from 2-naphthalenol and 1-(((2-pyridinylmethyl)imino)methyl)- (C1 and C2) were synthesized.

Purpose of the Study:

• To investigate the anti-cancer mechanisms of novel Cu2+ compounds (C1 and C2).
• To evaluate their potential as multi-targeted antitumor agents against human cancer cell lines.

Main Methods:

• Assessment of antiproliferative activity in three human cancer cell lines.
• Evaluation of toxicity against A-549 cells.
• Analysis of reactive oxygen species (ROS) generation and cell cycle arrest.
• Investigation of apoptosis and autophagy pathway activation.
• Assessment of endoplasmic reticulum stress induction and topoisomerase-1 inhibition.

Main Results:

• C1 and C2 demonstrated significant antiproliferative activity, outperforming Cisplatin in vitro.
• The Cu2+ complexes induced cell cycle arrest at the G0/G1 phase.
• Reactive oxygen species (ROS) generation was identified as a key mechanism of action.
• Apoptotic and autophagic pathways were activated in A-549 cells.
• Endoplasmic reticulum stress, topoisomerase-1 inhibition, and ROS-mediated DNA damage were observed.

Conclusions:

• The synthesized Cu2+ complexes (C1 and C2) are effective multi-targeted antitumor agents.
• ROS-mediated targeting of multiple cancer cell signaling pathways represents a viable strategy for cancer growth inhibition.