KEY TAKEAWAYS
- The study aimed to assess the effects of L-Theanine over chemoresistance in patients with lung cancer.
- L-Theanine improves DDP chemoresistance by regulating STAT3/NOTCH1/BMAL1, reducing stemness, and inhibiting migration.
L-Theanine- an amino acid derived from green tea, which is non-proteogenic, has been regarded as an anti-cancer candidate, recently. However, there is still limited information available on its role in the development of chemoresistance in cancer is still unknown and the molecular mechanism is required to be unveiled.
Wenjing Jin and the team designed this study to evaluate the effects of L-Theanine on lung cancer chemoresistance.
Researchers validated the effects of L-Theanine on chemoresistance in lung cancer using various assays like cell counting Kit-8 (CCK-8) assay, transwell assay, and in vitro tumor spheroid formation assay.
They assessed the protein expression through polymerase chain reaction (PCR) and western blotting. To evaluate the differential expression induced by L-Theanine, they employed RNA-sequencing (RNA-seq) and bioinformatics analysis. In addition to that BMAL1 knockdown and overexpression were achieved using a lentivirus-mediated transfection system.
Results indicated that L-Theanine enhanced chemoresistance to cis-diamminedichloroplatinum (DDP) and reduced stemness in DDP-resistant lung cancer cells, but not in non-resistant lung cancer cells. The RNA-seq analysis results indicated that the STAT3/NOTCH1 pathway was a potential dominant signaling pathway responsible for improving the hemoresistance in DDP-resistant lung cancer by L-Theanine.
The L-Theanine blocked the migration and stemness activation of DDP-resistant lung cancer cells by regulating the expression of STAT3/NOTCH1/BMAL1 signaling-induced stemness markers and inhibiting the expression levels of drug resistance-related genes.
Furthermore, a combination of L-Theanine and Stat3 blockade synergistically improved chemoresistance in DDP-resistant lung cancer.
The study concluded that L-Theanine improved chemoresistance by regulating STAT3/NOTCH1/BMAL1 signaling, reducing stemness, and inhibiting the migration of DDP-resistant lung cancer cells. The findings might provide insight into the therapeutic alternatives for overcoming chemoresistance in cancers, including lung cancer.
The study was funded by Pudong new area Science, Technology and Economy Commission.
Source: https://pubmed.ncbi.nlm.nih.gov/38940036/
Jin W., Su L., You H., et al. (2024). “L-Theanine Inhibits Chemoresistance of Lung Cancer Cells to Cisplatin by Regulating STAT3/NOTCH1-BMAL1 Signaling.” Front Biosci (Landmark Ed). 2024 Jun 21;29(6):226. doi: 10.31083/j.fbl2906226. PMID: 38940036.
