Hydrazone copper(II) complexes suppressed lung adenocarcinoma by activating multiple anticancer pathway

Area of Science:

• Inorganic Chemistry
• Medicinal Chemistry
• Cancer Research

Background:

• Activating multiple anti-cancer pathways is a key strategy for effective tumor treatment.
• Hydrazone copper complexes are being explored for their therapeutic potential.

Purpose of the Study:

• To synthesize and evaluate the anti-lung cancer activities of novel binuclear and mononuclear hydrazone-copper(II) complexes.
• To compare the efficacy of these complexes against cisplatin and assess their selectivity towards cancer cells.

Main Methods:

• Synthesis of two binuclear ([Cu2(HL1)2Cl2] 1 and [Cu2(HL1)2Br2] 2) and two mononuclear ([Cu(HL2)Cl]·CH3OH 3 and [Cu(HL2)(H2O)Br]·2H2O 4) Cu(II) complexes.
• In vitro cytotoxicity evaluation using MTT assays on A549 lung cancer cells.
• In vivo efficacy assessment in A549 tumor-bearing mice xenograft models.
• Hemolytic activity assays.

Main Results:

• All synthesized Cu(II) complexes exhibited superior anticancer activity compared to cisplatin.
• Complex 3 demonstrated selective toxicity towards A549 cancer cells over normal cells.
• Complex 3 showed comparable hemolytic activity to cisplatin and confirmed antitumor capabilities in vivo.
• Complex 3 effectively eradicated lung tumor cells via multiple pathways, including cuproptosis.

Conclusions:

• Hydrazone-copper(II) complexes, particularly complex 3, represent a promising avenue for lung cancer treatment.
• Complex 3's selective toxicity, low toxicity, and in vivo efficacy highlight its therapeutic potential.
• The induction of multiple anticancer pathways, including cuproptosis, by complex 3 provides a novel treatment strategy.