Lipophilic Fe(III)-Complex with Potent Broad-Spectrum Anticancer Activity and Ability to Overcome Pt Resistance in A2780cis Cancer Cells

Autor: Nalin Abeydeera, Morgan Stilgenbauer, Bishnu D. Pant, Khalil Mudarmah, Thiloka M. Dassanayake, Yao-Rong Zheng, Songping D. Huang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Molecules, Vol 28, Iss 13, p 4917 (2023)
Druh dokumentu: article
ISSN: 1420-3049
DOI: 10.3390/molecules28134917
Popis: Although iron is essential for all forms of life, it is also potentially toxic to cells as the increased and unregulated iron uptake can catalyze the Fenton reaction to produce reactive oxygen species (ROS), leading to lipid peroxidation of membranes, oxidation of proteins, cleavage of DNA and even activation of apoptotic cell death pathways. We demonstrate that Fe(hinok)3 (hinok = 2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one), a neutral Fe(III) complex with high lipophilicity is capable of bypassing the regulation of iron trafficking to disrupt cellular iron homeostasis; thus, harnessing remarkable anticancer activity against a panel of five different cell lines, including Pt-sensitive ovarian cancer cells (A2780; IC50 = 2.05 ± 0.90 μM or 1.20 μg/mL), Pt-resistant ovarian cancer cells (A2780cis; IC50 = 0.92 ± 0.73 μM or 0.50 μg/mL), ovarian cancer cells (SKOV-3; IC50 = 1.23 ± 0.01 μM or 0.67 μg/mL), breast cancer cells (MDA-MB-231; IC50 = 3.83 ± 0.12 μM or 2.0 μg/mL) and lung cancer cells (A549; IC50 = 1.50 ± 0.32 μM or 0.82 μg/mL). Of great significance is that Fe(hinok)3 exhibits unusual selectivity toward the normal HEK293 cells and the ability to overcome the Pt resistance in the Pt-resistant mutant ovarian cancer cells of A2780cis.
Databáze: Directory of Open Access Journals
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