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Lipophilic Fe(III)-Complex with Potent Broad-Spectrum Anticancer Activity and Ability to Overcome Pt Resistance in A2780cis Cancer Cells.
Abeydeera, Nalin; Stilgenbauer, Morgan; Pant, Bishnu D; Mudarmah, Khalil; Dassanayake, Thiloka M; Zheng, Yao-Rong; Huang, Songping D.
Afiliación
  • Abeydeera N; Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA.
  • Stilgenbauer M; Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA.
  • Pant BD; Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA.
  • Mudarmah K; Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA.
  • Dassanayake TM; Department of Chemistry, Jazan University, Jazan 45142, Saudi Arabia.
  • Zheng YR; Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA.
  • Huang SD; Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA.
Molecules ; 28(13)2023 Jun 22.
Article en En | MEDLINE | ID: mdl-37446578
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Antineoplásicos Límite: Female / Humans Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Antineoplásicos Límite: Female / Humans Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza