KEY TAKEAWAYS
- The study aimed to evaluate the role of a novel chalcone derivative of tetramethylpyrazine, HCTMPPK, in lung adenocarcinoma.
- The study’s findings suggested that HCTMPPK could be a promising candidate for lung cancer therapy by acting as a potential MELK inhibitor.
Lung adenocarcinoma stands as one of the primary causes of cancer-related deaths globally. Various anti-inflammatory herbs, such as tetramethylpyrazine, have demonstrated potential in combating tumors.
Yan Ma and the team aimed to examine the function of a new chalcone derivative of tetramethylpyrazine, termed HCTMPPK, in lung adenocarcinoma.
The study investigated the effects of HCTMPPK on cell proliferation, apoptosis, and invasion through in-vitro assays, including CCK-8, colony formation, flow cytometry, transwell, and wound-healing assays. The therapeutic potential of HCTMPPK was assessed in vivo. To identify the target molecules of HCTMPPK, researchers employed a network pharmacology approach and conducted molecular docking studies, followed by experiments to confirm these candidate molecules.
The results revealed that HCTMPPK effectively suppressed the proliferative activity and migration of A549 cells and enhanced apoptosis in a concentration-dependent manner. In vivo experiments showed significant inhibition of tumor growth by HCTMPPK. Mechanistically, HCTMPPK down-regulated Bcl-2 and MMP-9 while up-regulating Bax and cleaved-caspase-3. Subsequently, 601 overlapping DEGs were identified from LUAD patients in TCGA and GEO databases. Fifteen hub genes were then identified through the PPI network and CytoHubba analysis. Finally, molecular docking studies and validation experiments confirmed MELK as the targeted site of HCTMPPK.
The study’s findings suggested that HCTMPPK shows promise as a potential MELK inhibitor and could emerge as a promising therapy candidate for lung cancer.
Funding was provided by the Open found project of NMPA Key Laboratory for Quality Research and Evaluation of Traditional Marine Chinese Medicine, Traditional Chinese Medicine Science and Technology Project of Qingdao Municipal Health Commission, Shinan District Science and Technology Plan Project, and Zaozhuang Medicine and Health Science and Technology Development Program Project.
Source: https://pubmed.ncbi.nlm.nih.gov/38737331/
Ma Y, Cui Q, Zhu W, et al. (2024). “A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK.” Drug Des Devel Ther. 2024 May 7;18:1531-1546. doi: 10.2147/DDDT.S449139. PMID: 38737331; PMCID: PMC11088378.
