Acetylshikonin Induces Necroptosis in Lung Cancer | Aging-US

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January 4, 2024

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  • Aging-US published this trending research paper on December 19, 2023, in Volume 15, Issue 24, entitled, “Acetylshikonin induces necroptosis via the RIPK1/RIPK3-dependent pathway in lung cancer" by researchers from the Division of Chest Medicine, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan; Translational Medicine Center, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan; Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi City 613016, Taiwan; Department of Nursing, Division of Basic Medical Sciences, Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi City 613016, Taiwan; Department of Safety Health and Environmental Engineering, Ming Chi University of Technology, New Taipei City 243303, Taiwan; Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan; Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi 613016, Taiwan; School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei 110301, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404328, Taiwan. DOI - https://doi.org/10.18632/aging.205316 Corresponding authors - Ju-Fang Liu - jufangliu@tmu.edu.tw Abstract Despite advances in therapeutic strategies, lung cancer remains the leading cause of cancer-related death worldwide. Acetylshikonin is a derivative of the traditional Chinese medicine Zicao and presents a variety of anticancer properties. However, the effects of acetylshikonin on lung cancer have not been fully understood yet. This study explored the mechanisms underlying acetylshikonin-induced cell death in non-small cell lung cancer (NSCLC). Treating NSCLC cells with acetylshikonin significantly reduced cell viability, as evidenced by chromatin condensation and the appearance of cell debris. Acetylshikonin has also been shown to increase cell membrane permeability and induce cell swelling, leading to an increase in the population of necrotic cells. When investigating the mechanisms underlying acetylshikonin-induced cell death, we discovered that acetylshikonin promoted oxidative stress, decreased mitochondrial membrane potential, and promoted G2/M phase arrest in lung cancer cells. The damage to NSCLC cells induced by acetylshikonin resembled results involving alterations in the cell membrane and mitochondrial morphology. Our analysis of oxidative stress revealed that acetylshikonin induced lipid oxidation and down-regulated the expression of glutathione peroxidase 4 (GPX4), which has been associated with necroptosis. We also determined that acetylshikonin induces the phosphorylation of receptor-interacting serine/threonine-protein kinase 1 (RIPK1)/RIPK3 and mixed lineage kinase domain-like kinase (MLKL). Treatment with RIPK1 inhibitors (necrostatin-1 or 7-Cl-O-Nec-1) significantly reversed acetylshikonin-induced MLKL phosphorylation and NSCLC cell death. These results indicate that acetylshikonin activated the RIPK1/RIPK3/MLKL cascade, leading to necroptosis in NSCLC cells. Our findings indicate that acetylshikonin reduces lung cancer cells by promoting G2/M phase arrest and necroptosis. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205316 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, human lung cancer, acetylshikonin, ROS, necroptosis About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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