Lei Zhang1,2, Wen-Xu Chen1,3, Ling-Li Li2, Yu-Zhu Cao1, Ya-Di Geng1,2, Xiao-Jun Feng1,2, Ai-Yun Wang4, Zhao-Lin Chen1,2, Yin Lu4, Ai-Zong Shen1,2,3. 1. Department of Pharmacy, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Provincial Hospital, Hefei, China. 2. Department of Pharmacy, Anhui Provincial Hospital, Anhui Medical University, Hefei, China. 3. Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China. 4. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Abstract
Background: Targeting inflammatory microenvironment is a promising anti-tumor strategy. Paeonol is a phenolic compound with effective anti-inflammatory and anti-tumor properties. However, the effects of paeonol on non-small cell carcinoma (NSCLC) have not been fully investigated. Here, we evaluated the effects of paeonol on proliferation and metastasis of NSCLC and elucidated the underlying mechanisms. Methods: The effects of paeonol on inflammatory cytokines were determined by cell proliferation and ELISA assays. Assays of wound healing, single cell migration and perforation invasion were used to evaluate migration and invasion of NSCLC cells. Expression of marker proteins in epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) family enzymes were detected by Western blot assays. Nude mouse A549 cells transplantation tumor model was used to study the anti-lung cancer effects of paeonol in vivo. TUNEL stanining were used to detect the apoptosis of tumor cells in A549 lung cancer mice, and Ki67 analysis was used to detect the proliferation of tumor cells in A549 lung cancer mice. Immunohistochemistry was used to detect the effects of paeonol on signaling molecules in tumor tissues. Results: Paeonol inhibited A549 cancer cell migration and invasion in vitro. Paeonol inhibited secreaion of inflammatory cytokines in A549 cells, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and transforming growth factor (TGF)-β. Paeonol altered the expression of marker proteins involved in EMT and MMP family enzymes. In addition, paeonol inhibited the transcriptional activity of nuclear factor-κB (NF-κB) and phosphorylation of signal transducers and activators of transcription 3 (STAT3). Paeonol inhibited the growth of A549 cells transplanted tumors in nude mice. Conclusion: Paeonol potently inhibited NSCLC cell growth, migration and invasion associated with disruption of STAT3 and NF-κB pathways, suggesting that it could be a promising anti-metastatic candidate for tumor chemotherapy.
Background: Targeting inflammatory microenvironment is a promising anti-tumor strategy. Paeonol is a phenolic compound with effective anti-inflammatory and anti-tumor properties. However, the effects of paeonol on non-small cell carcinoma (NSCLC) have not been fully investigated. Here, we evaluated the effects of paeonol on proliferation and metastasis of NSCLC and elucidated the underlying mechanisms. Methods: The effects of paeonol on inflammatory cytokines were determined by cell proliferation and ELISA assays. Assays of wound healing, single cell migration and perforation invasion were used to evaluate migration and invasion of NSCLC cells. Expression of marker proteins in epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) family enzymes were detected by Western blot assays. Nude mouseA549 cells transplantation tumor model was used to study the anti-lung cancer effects of paeonol in vivo. TUNEL stanining were used to detect the apoptosis of tumor cells in A549lung cancermice, and Ki67 analysis was used to detect the proliferation of tumor cells in A549lung cancermice. Immunohistochemistry was used to detect the effects of paeonol on signaling molecules in tumor tissues. Results:Paeonol inhibited A549cancer cell migration and invasion in vitro. Paeonol inhibited secreaion of inflammatory cytokines in A549 cells, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and transforming growth factor (TGF)-β. Paeonol altered the expression of marker proteins involved in EMT and MMP family enzymes. In addition, paeonol inhibited the transcriptional activity of nuclear factor-κB (NF-κB) and phosphorylation of signal transducers and activators of transcription 3 (STAT3). Paeonol inhibited the growth of A549 cells transplanted tumors in nude mice. Conclusion:Paeonol potently inhibited NSCLC cell growth, migration and invasion associated with disruption of STAT3 and NF-κB pathways, suggesting that it could be a promising anti-metastatic candidate for tumor chemotherapy.
Authors: Matthew R Trendowski; Omar El Charif; Paul C Dinh; Lois B Travis; M Eileen Dolan Journal: Clin Cancer Res Date: 2018-10-10 Impact factor: 12.531
Authors: McA Wouters; E M Dijkgraaf; M L Kuijjer; E S Jordanova; H Hollema; Mjp Welters; Jjm van der Hoeven; T Daemen; J R Kroep; H W Nijman; S H van der Burg Journal: Oncoimmunology Date: 2015-01-07 Impact factor: 8.110
Authors: Abdulla Y Al-Taher; Mohamed A Morsy; Rehab A Rifaai; Nagwa M Zenhom; Seham A Abdel-Gaber Journal: Mediators Inflamm Date: 2020-02-10 Impact factor: 4.711
Authors: Mohamed A Morsy; Azza A K El-Sheikh; Sara Mohamed Naguib Abdel-Hafez; Mahmoud Kandeel; Seham A Abdel-Gaber Journal: Front Pharmacol Date: 2022-02-04 Impact factor: 5.810
Authors: Iwona Radziejewska; Katarzyna Supruniuk; Michał Tomczyk; Wiktoria Izdebska; Małgorzata Borzym-Kluczyk; Anna Bielawska; Krzysztof Bielawski; Anna Galicka Journal: Int J Mol Sci Date: 2022-08-02 Impact factor: 6.208