Background: Aberrant signal transducer and activator of transcription 3 (STAT-3) molecular signaling elicit hepatocellular carcinoma (HCC) in humans. Therefore, targeting STAT-3 is considered as an attractive option towards suppression of HCC in humans.
Objective: Our objective is to identify a potential small molecule inhibitor that can specifically target STAT-3 and suppress HCC.
Methods: In this study, we analyze a group of sesquiterpene lactone (STL) candidates that has been recently reported in preclinical trials against cancer by a unified computational and experimental approach.
Results: Our virtual analysis of the STL candidates revealed Artesunate (ATS) as the best potential inhibitor of STAT-3 with comparable potency to specific inhibitor S3I-201. We also observed that ATS inhibited IL-6 driven STAT-3-DNA binding activity with comparable potency to S3I-201 in a cell free system. Furthermore ATS was observed to interfere with STAT-3 dimerization and suppression of both constitutive and IL-6 inducible STAT-3 in vitro. Nevertheless, we also observed that ATS modulated STAT-3 dependent targets (procaspase-3, Bcl-xl and survivin) favoring occurrence of apoptosis in vitro. Overall, the putative inhibition of STAT-3 by ATS suggested its capacity to interfere with STAT-3 dimerization by binding to the SH2 domain of STAT-3 monomer. It resulted in suppression of STAT-3 and also favored promotion of in vitro cells towards apoptosis. Consequently, ATS also exhibited selective cytotoxicity of cancer cells over normal cells in vitro.
Conclusion: All the above observations substantiated by unified computational and in vitro experimental approaches suggested its potential role as a therapeutic anti-cancer agent against HCC.
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http://dx.doi.org/10.2174/1568026616666160212122820 | DOI Listing |
J Inflamm Res
January 2025
Department of Otorhinolaryngology-Head & Neck Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
Introduction: Prolonged psychological stress is closely associated with cancer due to its role in promoting the release of stress hormones through the sustained activation of the sympathetic-adrenal-medullary system. These hormones interact with receptors on inflammatory cells, leading to the activation of key signaling pathways, including the transcription factors signal transducer and activator of transcription 3 (STAT-3) and kappa-light-chain-enhancer of activated B cells (NF-κB). These factors drive the production of pro-inflammatory substances, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which can influence the initiation and progression of cancer.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA. Electronic address:
Global healthcare systems are under tremendous strain due to the increasing prevalence of neurodegenerative disorders. Growing data suggested that overconsumption of high-fat/high-carbohydrates diet (HFHCD) is associated with enhanced incidence of metabolic alterations, neurodegeneration, and cognitive dysfunction. Functional foods have gained prominence in curbing metabolic and neurological deficits.
View Article and Find Full Text PDFIran J Basic Med Sci
January 2025
Department of Animal Nutrition and Nutritional Disorders, Faculty of Veterinary Medicine, Ataturk University, Erzurum 25240, Turkey.
Objectives: This experiment was carried out to investigate the protective effects of curcumin (CUR) on testicular damage induced by the valproic acid (VPA) administration.
Materials And Methods: Male Wistar-Albino rats (n=28, 250-300 g) were randomly divided into four groups: Control (1 ml saline, oral), VPA (500 mg/kg, IP), CUR (200 mg/kg, oral), or VPA+CUR (500 mg/kg, VPA, IP plus 200 mg/kg CUR, oral). The treatments were applied for 14 days.
RSC Adv
January 2025
Department of Pharmaceutical Sciences, Maharshi Dayanand University Rohtak 124001 India
Cancer is a major global concern. Despite considerable advancements in cancer therapy and control, there are still large gaps and requirements for development. In recent years, various naturally occurring anticancer drugs have been derived from natural resources, such as alkaloids, glycosides, terpenes, terpenoids, flavones, and polyphenols.
View Article and Find Full Text PDFAdv Clin Exp Med
January 2025
Department of Hematology, Rheumatology and Immunology, The First People's Hospital of Xianyang, China.
Background: Leukemia may form at any age, from newborns to the elderly, and accounts for considerable mortality worldwide.
Objectives: Nerolidol (NRD) is isolated from the aromatic florae oils and was found to have anticancer activities. However, the role of NRD in antiproliferative and apoptosis actions in acute lymphoblastic leukemia (ALL) is unclear.
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