Bioactive Materials (Mar 2025)
TClC effectively suppresses the growth and metastasis of NSCLC via polypharmacology
- Jing Lu,
- Ying Zhang,
- Chunyan Yan,
- Jingwen Liu,
- Dan Qi,
- Yue Zhou,
- Qinwen Wang,
- Juechen Yang,
- Jing Jiang,
- Benhao Wu,
- Meiling Yang,
- Weiwei Zhang,
- Xin Zhang,
- Xiaoyu Shi,
- Yan Zhang,
- Kun Liu,
- Yongcai Liang,
- Chaoyang Wang,
- Hanyu Yang,
- Yuqing Gao,
- Yuping Sun,
- Ronghu Ke,
- Jason H. Huang,
- Min Wu,
- Hongbo Wang,
- Chunlei Li,
- Shuang Zhou,
- Bin Guo,
- Erxi Wu,
- Guoying Zhang
Affiliations
- Jing Lu
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China
- Ying Zhang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China; Shandong Yingdong Yinghao Biotechnology Inc., Yantai, Shandong, 264670, China; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 58105, USA
- Chunyan Yan
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China; Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, Shandong, 264000, China
- Jingwen Liu
- Department of Pharmacological & Pharmaceutical Sciences, University of Houston, Houston, TX, 77204, USA
- Dan Qi
- Neuroscience Institute and Department of Neurosurgery, Baylor Scott & White Health, Temple, TX, 76502, USA; Department of Neurosurgery, Baylor College of Medicine, Temple, TX, 76502, USA
- Yue Zhou
- Department of Statistics, North Dakota State University, Fargo, ND, 58102, USA
- Qinwen Wang
- The Center of Non-Traumatic Treatment and Diagnosis of Tumor, Binzhou Medical College affiliated The PLA 107 Hospital, Yantai, Shandong, 264002, China; Outpatient Department, No. 26 Rest Center for Retired Cadres, Haidian district, Beijing, 100036, China
- Juechen Yang
- Department of Biomedical Informatics, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- Jing Jiang
- RemeGen, Ltd, Yantai, 264000, Shandong, China; Department of Pharmacology, Binzhou Medical University, Yantai, 264003, Shandong, China
- Benhao Wu
- Shandong Yingdong Yinghao Biotechnology Inc., Yantai, Shandong, 264670, China
- Meiling Yang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China; Shandong Yingdong Yinghao Biotechnology Inc., Yantai, Shandong, 264670, China
- Weiwei Zhang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China; Shandong Yingdong Yinghao Biotechnology Inc., Yantai, Shandong, 264670, China
- Xin Zhang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China; Shandong Yingdong Yinghao Biotechnology Inc., Yantai, Shandong, 264670, China
- Xiaoyu Shi
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China; Shandong Yingdong Yinghao Biotechnology Inc., Yantai, Shandong, 264670, China
- Yan Zhang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China; Shandong Yingdong Yinghao Biotechnology Inc., Yantai, Shandong, 264670, China
- Kun Liu
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China
- Yongcai Liang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China
- Chaoyang Wang
- Department of Thoracic Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong, 264000, China
- Hanyu Yang
- Shiyao Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., LTD., State Key Laboratory of New Pharmaceutical Preparations and Excipients, Shijiazhuang, 050035, China
- Yuqing Gao
- Shiyao Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., LTD., State Key Laboratory of New Pharmaceutical Preparations and Excipients, Shijiazhuang, 050035, China
- Yuping Sun
- Phase I Clinical Trial Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250013, China
- Ronghu Ke
- Neuroscience Institute and Department of Neurosurgery, Baylor Scott & White Health, Temple, TX, 76502, USA
- Jason H. Huang
- Neuroscience Institute and Department of Neurosurgery, Baylor Scott & White Health, Temple, TX, 76502, USA; College of Medicine, Texas A&M University, College Station, TX, 77843, USA; Department of Neurosurgery, Baylor College of Medicine, Temple, TX, 76502, USA
- Min Wu
- Drug Discovery Center, Wenzhou Institute University of Chinese Academy of Sciences, Wenzhou, 325001, China; Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 646000, China
- Hongbo Wang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China
- Chunlei Li
- Shiyao Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., LTD., State Key Laboratory of New Pharmaceutical Preparations and Excipients, Shijiazhuang, 050035, China; Corresponding author.
- Shuang Zhou
- Department of Pharmacological & Pharmaceutical Sciences, University of Houston, Houston, TX, 77204, USA; Corresponding author.
- Bin Guo
- Department of Pharmacological & Pharmaceutical Sciences, University of Houston, Houston, TX, 77204, USA; Corresponding author.
- Erxi Wu
- Neuroscience Institute and Department of Neurosurgery, Baylor Scott & White Health, Temple, TX, 76502, USA; College of Medicine, Texas A&M University, College Station, TX, 77843, USA; College of Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station, TX, 77843, USA; Department of Neurosurgery, Baylor College of Medicine, Temple, TX, 76502, USA; LIVESTRONG Cancer Institutes and Department of Oncology, Dell Medical School, the University of Texas at Austin, Austin, TX, 78712, USA; Corresponding author. Neuroscience Institute and Department of Neurosurgery, Baylor Scott & White Health, Temple, TX, 76502, USA.
- Guoying Zhang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China; Corresponding author.
- Journal volume & issue
-
Vol. 45
pp. 567 – 583
Abstract
Despite significant advances in targeted therapies and immunotherapies, non-small cell lung cancer (NSCLC) continues to present a global health challenge, with a modest five-year survival rate of 28 %, largely due to the emergence of treatment-resistant and metastatic tumors. In response, we synthesized a novel bioactive compound, ethyl 6-chlorocoumarin-3-carboxylyl L-theanine (TClC), which significantly inhibited NSCLC growth, epithelial mesenchymal transition (EMT), migration, and invasion in vitro and tumor growth and metastasis in vivo without inducing toxicity. TClC disrupts autocrine loops that promote tumor progression, particularly in stem-like CD133-positive NSCLC (CD133+ LC) cells, which are pivotal in tumor metastasis. Through targeted molecular assays, we identified direct binding targets of TClC, including Akt, NF-κB, β-catenin, EZH2, and PD-L1. This interaction not only suppresses the expression of oncogenic factors and cancer stem cell markers but also downregulates the expression of a multidrug resistance transporter, underscoring the compound's polypharmacological potential. These results position TClC as a promising candidate for NSCLC treatment, signaling a new era in the development of cancer therapies that directly target multiple critical cancer pathways.
