{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:29:12Z","timestamp":1791322152778,"version":"4.3.1"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 \u00b1 0.90 \u03bcM or 1.20 \u03bcg\/mL), Pt-resistant ovarian cancer cells (A2780cis; IC50 = 0.92 \u00b1 0.73 \u03bcM or 0.50 \u03bcg\/mL), ovarian cancer cells (SKOV-3; IC50 = 1.23 \u00b1 0.01 \u03bcM or 0.67 \u03bcg\/mL), breast cancer cells (MDA-MB-231; IC50 = 3.83 \u00b1 0.12 \u03bcM or 2.0 \u03bcg\/mL) and lung cancer cells (A549; IC50 = 1.50 \u00b1 0.32 \u03bcM or 0.82 \u03bcg\/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.<\/jats:p>","DOI":"10.3390\/molecules28134917","type":"journal-article","created":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T02:34:07Z","timestamp":1687487647000},"page":"4917","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Lipophilic Fe(III)-Complex with Potent Broad-Spectrum Anticancer Activity and Ability to Overcome Pt Resistance in A2780cis Cancer Cells"],"prefix":"10.3390","volume":"28","author":[{"given":"Nalin","family":"Abeydeera","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5575-3577","authenticated-orcid":false,"given":"Morgan","family":"Stilgenbauer","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishnu D.","family":"Pant","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalil","family":"Mudarmah","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA"},{"name":"Department of Chemistry, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiloka M.","family":"Dassanayake","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Rong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songping D.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Kent State University, Kent, OH 44240, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/222385a0","article-title":"Platinum compounds: A new class of potent antitumour agents","volume":"222","author":"Rosenberg","year":"1969","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/205698a0","article-title":"Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode","volume":"205","author":"Rosenberg","year":"1965","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1021\/cr980421n","article-title":"Structure, recognition, and processing of cisplatin\u2013DNA adducts","volume":"99","author":"Jamieson","year":"1999","journal-title":"Chem. 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