TClC effectively suppresses the growth and metastasis of NSCLC via polypharmacology

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 <i>in vitro</i> and tumor growth and metastasis <i>in vivo</i> 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.

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Publication Details

Journal
Bioactive Materials
Published
2024-12-13
DOI
https://doi.org/10.1016/j.bioactmat.2024.11.019
Citations
2
Primary Topic
Cancer Mechanisms and Therapy
Type
article
Field-Weighted Citation Impact
0.85
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article

TClC effectively suppresses the growth and metastasis of NSCLC via polypharmacology

Yunsong Liang, Yuqing Gao, Chunyan Yan, Jason H. Huang et al.
2 citations
Bioactive Materials
Cancer Mechanisms and Therapy
0.85
article

TClC effectively suppresses the growth and metastasis of NSCLC via polypharmacology

Yunsong Liang, Yuqing Gao, Chunyan Yan, Jason H. Huang, Benhao Wu, Bin Guo, Dan Qi, Erxi Wu, Yue Zhou, Min Wu, Xin Zhang, Chunlei Li, Hongbo Wang, Jingwen Liu, Weiwei Zhang, Yan Zhang, Shuang Zhou, Guoying Zhang, Ying Zhang, Xiaoyu Shi, Qinwen Wang, Juechen Yang, Meiling Yang, Yuping Sun, Jing Lu, Hanyu Yang, Kun Liu, Ronghu Ke, Jing Jiang, C Wang
article en
2 citations

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 <i>in vitro</i> and tumor growth and metastasis <i>in vivo</i> 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.

Bioactive MaterialsVol. 45
Cincinnati Children's Hospital Medical Center (US), Livestrong Foundation (US), Binzhou Medical University (CN), Wenzhou University (CN), Shandong University of Aeronautics (CN), Baylor College of Medicine (US), Yantai University (CN), Sichuan University (CN), Temple College (US), Yuhuangding Hospital (CN), Baylor Scott & White Medical Center - Temple (US), Shijiazhuang Yiling Pharmaceutical (China) (CN), Baylor Scott & White Health (US), Beijing Haidian Hospital (CN), Shandong First Medical University (CN), University of Houston (US), North Dakota State University (US), Shandong Institute of Business and Technology (CN), Texas A&M University (US), University of Cincinnati Medical Center (US)
Zero hunger
Openalex Percentile: Top 24%
Cancer Mechanisms and Therapy
0.85
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