@conference{
author = "Murganić, Blagoje and Kazimir, Aleksandar and Jelača, Sanja and Tanić, Nikola and Hey-Hawkins, Evamarie and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Estrogen receptor-posiƟ ve (ER+) breast cancer accounts for approximately 70% of all cases and, concordantly, anƟ -estrogen therapies present a leading therapeuƟ c choice. InteresƟ ngly, tamoxifen, which is the most commonly used drug, has also been proven eff ecƟ ve in hormone-independent forms of breast cancer, suggesƟ ng the existence of intracellular off -targets. Frequent acquisiƟ on of therapy resistance presents a plaƞ orm for the design of tamoxifen derivaƟ ves with a 2,2’-bipyridine unit enabling the coordinaƟ on of transiƟ on metal moieƟ es, such as copper(II) dichloride. Copper (Cu) is an essenƟ al element involved in the regulaƟ on of cellular growth and development. DisrupƟ on of its delicate homeostasis results in severe toxicity and hard medical condiƟ ons. Increased demand of cancer cells for this micronutrient makes it a valuable candidate for drug design in cancer treatment. The mechanism of acƟ on of Cu complexes is typically based on their ability to induce deadly oxidaƟ ve stress. This study evaluated the effi cacy of a copper–tamoxifen hybrid drug on a panel of breast cancer cell lines with varying receptor expression status. Material and Methods: The viability of breast adenocarcinoma cell lines MCF-7, MDA-MB-361, MDA-MB-231, 4T1 and glioma U251 was esƟ mated by MTT and CV assays. Flow cytometric analysis of cells stained with annexin V-FITC/propidium iodide, ApoStat, acridine orange, dihydrorhodamine 123 (DHR), dihydroethidium (DHE) or 4-amino-5-methylamino-2’,7’-difl uorofl uorescein diacetate (DAF) was used to evaluate cell death, caspase acƟ vity, autophagy, producƟ on of reacƟ ve oxygen and nitrogen species (ROS/RNS), respecƟ vely. Results: The Cu-tamoxifen hybrid drug displayed substanƟ ally higher hormone-receptor (HR) independent cytotoxic acƟ vity compared to previously reported metal complexes with a similar tamoxifen vector. Massive caspase-dependent apoptoƟ c cell death is parƟ ally aƩ enuated by an autophagic process that counteracts death signals. In contrast to the plaƟ num analogue, the copper-based tamoxifen derivaƟ ve reduces ROS/RNS that may be associated with the intracellular accumulaƟ on of the reduced form of CuI which is important for cuproptosis. Conclusion: This study demonstrates the potenƟ al of the copper–tamoxifen hybrid drug as an intriguing alternaƟ ve to commonly used plaƟ num complexes in treatment of cancer. Its safety and effi ciency will be further esƟ mated in vivo",
publisher = "Belgrade : Serbian Association for Cancer Research",
journal = "Oncology Insights",
title = "Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy",
number = "1",
pages = "95-95",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12639"
}
