Journal
MOLECULES
Volume 24, Issue 14, Pages -Publisher
MDPI
DOI: 10.3390/molecules24142544
Keywords
Cu(II) complex; 2-hydroxy-1-naphthaldehyde; cytotoxicity; anticancer mechanism
Funding
- Natural Science Foundation of China [21431001, 31460232]
- Natural Science Foundation of Guangxi [2017GXNSFEA198002, AD17129007]
- Guangxi Bagui scholar program [IRT_16R15]
- High-Level Innovation Team and Distinguished Scholar program of Guangxi universities
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Multi-targeting of oncoproteins by a single molecule represents an effectual, rational, and an alternative approach to target therapy. We carried out a systematic study to reveal the mechanisms of action of newly synthesized Cu2+ compounds of 2-naphthalenol and 1-(((2-pyridinylmethyl)imino)methyl)- (C1 and C2). The antiproliferative activity of the as-synthesized complexes in three human cancer cell lines indicates their potential as multi-targeted antitumor agents. Relatively, C1 and C2 showed better efficacy in vitro relative to Cisplatin and presented promising levels of toxicity against A-549 cells. On the whole, the Cu2+ complexes exhibited chemotherapeutic effects by generating reactive oxygen species (ROS) and arresting the cell cycle in the G(0)/G(1) phase by competent regulation of cyclin and cyclin-dependent kinases. Fascinatingly, the Cu2+ complexes were shown to activate the apoptotic and autophagic pathways in A-549 cells. These complexes effectively induced endoplasmic reticulum stress-mediated apoptosis, inhibited topoisomerase-1, and damaged cancer DNA through a ROS-mediated mechanism. The synthesized Cu2+ complexes established ROS-mediated targeting of multiple cell signaling pathways as a fabulous route for the inhibition of cancer cell growth.
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