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Laser-induced photoproducts altered CPZ structure, yielding favorable drug-like and ADMETox profiles, dose- and time-dependent cancer cytotoxicity, reduced toxicity in healthy cells, F-actin disruption, and excessive ROS generation, supporting therapeutic potential.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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approach does the study use to enhance chlorpromazine efficacy against breast cancer?","Question",{"text":63,"@type":64},"Chlorpromazine is irradiated with a 266 nm laser for varying durations, creating laser-generated photoproducts that are then evaluated for anticancer activity.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How are CPZ and its laser photoproducts characterized and assessed?",{"text":68,"@type":64},"The work uses UV-Vis and FTIR spectroscopy, followed by druglikeness and ADME-Tox predictions to evaluate expected pharmacological behavior.",{"name":70,"@type":61,"acceptedAnswer":71},"What do the in vitro results show regarding cancer cells versus healthy cells?",{"text":72,"@type":64},"Laser irradiation produces dose- and time-dependent cytotoxicity against MCF-7 breast cancer cells while showing reduced toxicity on the healthy MCF-12A cell 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\nEnhancement of chlorpromazine efficacy in breast cancer treatment by 266 nm laser irradiation  \nAna Maria Udrea1,2,3, Angela Staicu1􀀍, Adriana Smarandache1, Ionut Relu Andrei1, Madalina Andreea Badea4, Speranta Avram3, Mihail Lucian Pascu1,5,  \nRuxandra Angela Pirvulescu6 & Mihaela Balas4􀀍  \nBreast cancer remains a global health challenge, prompting interest in the anticancer properties of other drugs, including chlorpromazine (CPZ). This study presents a novel approach in breast cancer treatment using laser irradiated CPZ. CPZ dissolved in distilled water, was exposed to 266 nm laser irradiation for varying durations, characterized by UV-Vis and FTIR spectroscopy, followed by druglikeness and ADME-Tox predictions. In vitro assays evaluated the cytotoxicity and cellular effects on MCF-7 breast cancer cells, and compared with MCF-12 A healthy cell line. Laser irradiation altered CPZ molecular structure resulting in photoproducts with favourable drug-like properties and ADMETox profiles. In vitro evaluations demonstrate dose and irradiation time-dependent cytotoxicity against breast cancer cells, and reduced toxicity on healthy cell line. Significant alterations in F-actin organization, and excessive ROS generation were also proved, suggesting the potential of lasermodified CPZ for breast cancer therapy. This study introduces a novel approach to breast cancer treatment through laser irradiated CPZ, highlighting promising advancements in therapy and emphasizing the role of laser-generated compounds.  \nKeywords Chlorpromazine, Breast cancer, Drug repositioning, Laser-irradiated drugs, Antipsychotic drugs, ADME-Tox  \nBackground  \nDespite significant medical advancements, breast cancer remains a global health challenge. In 2020 breast cancer was the second leading cause of death for women, being responsible for, approximately 685,000 deaths which remains1. Alarmingly, predictions indicate a rise in new cases to over 3 million by 2040, with a potential death toll reaching 1 million, as reported by Arnold et al.2. The current treatments for cancer encompass surgery, chemotherapy, radiotherapy, endocrine therapy, and molecular targeted therapy3.  \nDue to their anticancer properties, there is a growing interest in exploring the potential role of antipsychotic drugs in cancer treatment. Both first generation (typical) and second generation (atypical) antipsychotic drugs, such as haloperidol, chlorpromazine (CPZ), pimozide, penfluridol, thioridazine,, aripiprazole, or clozapine, have shown anticancer effects4. For instance, aripiprazole, a second-generation antipsychotic, has demonstrated inhibitory activity in the MCF-7 breast cancer cell line, as highlighted by Badran et al. and Lee et al.5,6. Firstgeneration antipsychotics, including thioridazine, penfluridol, pimozide, CPZ, and trifluoperazine, also exhibit anti-cancer properties.  \nCPZ, a typical antipsychotic from the phenothiazines class, has shown notable anticancer effects, such as inducing apoptosis and inhibiting DNA synthesis4,7. Several studies have highlighted CPZ’s inhibitory activity  \n1National Institute for Laser, Plasma and Radiation Physics (INFLPR), 409 Atomistilor Street, Magurele 077125, Romania. 2Research Institute of the University of Bucharest (ICUB), University of Bucharest, 90-92 Sos. Panduri, Bucharest 050663, Romania. 3Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, Bucharest 050095, Romania. 4Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91–95 Splaiul Independentei, Bucharest 050095, Romania. 5Academy of Romanian Scientists, 3 Ilfov, Bucharest 050044, Romania. 6Carol Davila University of Medicine and Pharmacy, 37 Dionisie Lupu Street, Bucharest 020021, Romania. 􀀍 email: [angela.staicu@inflpr.ro](angela.staicu@inflpr.ro); [mihaela.balas@bio.unibuc.ro]","cbCainSh4hc9vrr2","https://ap.wps.com/l/cbCainSh4hc9vrr2","pdf",3490226,16,"English","# Background\n## Current burden of breast cancer\n## Antipsychotic drugs and anticancer effects\n## Rationale for chlorpromazine and laser modification","[{\"question\":\"What approach does the study use to enhance chlorpromazine efficacy against breast cancer?\",\"answer\":\"Chlorpromazine is irradiated with a 266 nm laser for varying durations, creating laser-generated photoproducts that are then evaluated for anticancer activity.\"},{\"question\":\"How are CPZ and its laser photoproducts characterized and assessed?\",\"answer\":\"The work uses UV-Vis and FTIR spectroscopy, followed by druglikeness and ADME-Tox predictions to evaluate expected pharmacological behavior.\"},{\"question\":\"What do the in vitro results show regarding cancer cells versus healthy cells?\",\"answer\":\"Laser irradiation produces dose- and time-dependent cytotoxicity against MCF-7 breast cancer cells while showing reduced toxicity on the healthy MCF-12A cell line.\"}]","Enhancement of chlorpromazine efficacy in breast cancer treatment by 266 nm laser irradiation | PDF",1789999687]