{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:23:06Z","timestamp":1788481386027,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"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>Cardamonin is a polyphenolic natural product that has been shown to possess cytotoxic activity against a variety of cancer cell lines. We previously reported the semi-synthesis of a novel Cu (II)\u2013cardamonin complex (19) that demonstrated potent antitumour activity. In this study, we further investigated the bioactivity of 19 against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective treatment for triple-negative breast cancer (TNBC) and pancreatic cancer, respectively. Results revealed that 19 abolished the formation of MDA-MB-468 and PANC-1 colonies, exerted growth-inhibitory activity, and inhibited cancer cell migration. Further mechanistic studies showed that 19 induced DNA damage resulting in gap 2 (G2)\/mitosis (M) phase arrest and microtubule network disruption. Moreover, 19 generated reactive oxygen species (ROS) that may contribute to induction of apoptosis, corroborated by activation of caspase-3\/7, PARP cleavage, and downregulation of Mcl-1. Complex 19 also decreased the expression levels of p-Akt and p-4EBP1, which indicates that the compound exerts its activity, at least in part, via inhibition of Akt signalling. Furthermore, 19 decreased the expression of c-Myc in PANC-1 cells only, which suggests that it may exert its bioactivity via multiple mechanisms of action. These results demonstrate the potential of 19 as a therapeutic agent for TNBC and pancreatic cancer.<\/jats:p>","DOI":"10.3390\/molecules26082166","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T05:52:00Z","timestamp":1618206720000},"page":"2166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Novel Semi-Synthetic Cu (II)\u2013Cardamonin Complex Exerts Potent Anticancer Activity against Triple-Negative Breast and Pancreatic Cancer Cells via Inhibition of the Akt Signaling Pathway"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6136-6741","authenticated-orcid":false,"given":"Md Shahadat","family":"Hossan","sequence":"first","affiliation":[{"name":"School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6031-4154","authenticated-orcid":false,"given":"Mohammed Khaled Bin","family":"Break","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail 81411, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey D.","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary M.","family":"Collins","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Wiart","sequence":"additional","affiliation":[{"name":"Centre for Natural and Medicinal Product Research, School of Pharmacy, University of Nottingham Malaysia, Semenyih 43500, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8966-3369","authenticated-orcid":false,"given":"Teng-Jin","family":"Khoo","sequence":"additional","affiliation":[{"name":"Centre for Natural and Medicinal Product Research, School of Pharmacy, University of Nottingham Malaysia, Semenyih 43500, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Alafnan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail 81411, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"ref_1","unstructured":"(2020, March 29). 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