Eriodictyol 5-O-methyl ether inhibits prostate cancer progression through targeting STAT3 signaling and inducing apoptosis and paraptosis.
| Title: | Eriodictyol 5-O-methyl ether inhibits prostate cancer progression through targeting STAT3 signaling and inducing apoptosis and paraptosis. |
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| Authors: | Yang MH; Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. Electronic address: didmini@naver.com.; Son NT; Institute of Chemistry, Vietnam Academy of Science and Technology (VAST), Hoang Quoc Viet, Caugiay, Hanoi, 10000, Viet Nam; Department of Chemistry, Graduate University of Science and Technology, VAST, Hoang Quoc Viet, Caugiay, Hanoi, 10000, Viet Nam; University of São Paulo (USP), School of Pharmaceutical Sciences of Ribeirão Preto, SP, Brazil. Electronic address: yamantson@gmail.com.; Bastos JK; University of São Paulo (USP), School of Pharmaceutical Sciences of Ribeirão Preto, SP, Brazil. Electronic address: jkbastos@fcfrp.usp.br.; Luyen ND; Institute of Natural Products Chemistry, VAST, Hoang Quoc Viet, Caugiay, Hanoi, 10000, Viet Nam. Electronic address: dinhluyen1085@gmail.com.; Linh NN; Faculty of Pharmacy, Thanh Do University, Kim Chung, Hoai Duc, Hanoi, 10000, Viet Nam. Electronic address: nnlinh@thanhdouni.edu.vn.; Ahn KS; Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. Electronic address: ksahn@khu.ac.kr. |
| Source: | Archives of biochemistry and biophysics [Arch Biochem Biophys] 2025 Apr; Vol. 766, pp. 110331. Date of Electronic Publication: 2025 Feb 07. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: United States NLM ID: 0372430 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0384 (Electronic) Linking ISSN: 00039861 NLM ISO Abbreviation: Arch Biochem Biophys Subsets: MEDLINE |
| Imprint Name(s): | Publication: : San Diego, CA : Elsevier; Original Publication: New York, NY : Academic Press |
| MeSH Terms: | STAT3 Transcription Factor*/metabolism ; Prostatic Neoplasms*/metabolism ; Prostatic Neoplasms*/pathology ; Prostatic Neoplasms*/drug therapy ; Apoptosis*/drug effects ; Signal Transduction*/drug effects ; Flavanones*/pharmacology ; Flavanones*/chemistry ; Antineoplastic Agents*/pharmacology; Reactive Oxygen Species/metabolism ; Cell Proliferation/drug effects ; Endoplasmic Reticulum Stress/drug effects ; Janus Kinase 2/metabolism ; Male ; Humans ; Cell Line, Tumor ; Disease Progression ; Paraptosis |
| Abstract: | Prostate cancer ranks as one of the most prevalent cancers among men and is a major cause of cancer-related mortality globally This study aims to elucidate the molecular mechanisms underlying the anti-cancer effects of eriodictyol 5-O-methyl ether (ERIO) on prostate cancer cells, focusing on its impact on STAT3 signaling, apoptosis, and paraptosis. ERIO exhibited significant cytotoxicity against DU145, PC-3, and LNCaP cells. It suppressed constitutive and IL-6-induced STAT3 activation by inhibiting the phosphorylation of JAK1, JAK2, and Src kinases. ERIO upregulated SHP-2 expression, leading to the dephosphorylation of STAT3. ERIO induced apoptosis, evidenced by increased caspase-3 and PARP cleavage, and paraptosis, characterized by increased ROS production, decreased mitochondrial membrane potential, and ER stress. The antioxidant NAC reversed the effects of ERIO, highlighting the importance of oxidative stress in its anti-cancer activity. ERIO effectively inhibited prostate cancer cell growth by targeting STAT3 signaling and inducing both apoptosis and paraptosis. These findings suggest that ERIO has significant therapeutic potential for prostate cancer treatment and warrant further investigation in in vivo and clinical studies.; (Copyright © 2025. Published by Elsevier Inc.) |
| Competing Interests: | Declaration of competing interest The authors have no conflicts of interest to declare. |
| Contributed Indexing: | Keywords: Apoptosis; Autophagy; Eriodictyol 5-O-methyl ether; SHP-2; STAT3 |
| Substance Nomenclature: | 0 (STAT3 Transcription Factor); 0 (STAT3 protein, human); 0 (Flavanones); 0 (Antineoplastic Agents); Q520486B8Y (eriodictyol); 0 (Reactive Oxygen Species); EC 2.7.10.2 (Janus Kinase 2) |
| Entry Date(s): | Date Created: 20250209 Date Completed: 20250506 Latest Revision: 20250506 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.abb.2025.110331 |
| PMID: | 39924141 |
| Database: | MEDLINE |
Journal Article