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Antiproliferative and antitumorigenic activity of Toona sinensis leaf extracts in lung adenocarcinoma
Chih-Jen Yang1, Yu-Jung Huang, Cheng-Yuan Wang
1Department of Internal Medicine, Kaohsiung Medical University Hospital, Department of Internal Medicine, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract:
Toona sinensis is a traditional Chinese herb, and the extracts of T. sinensis leaf possess a variety of biological functions. This study attempted to test the antiproliferative effect of TSL-1 (a bioactive fraction of T. sinensis) in H441 cells (lung adenocarcinoma). The data showed that the antiproliferative effect of TSL-1 on H441 cells is prominent using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSL-1-induced apoptosis was confirmed by cell morphology, sub-G(1) peak accumulation, cleavage of poly(ADP)-ribose polymerase, and propidium iodide-annexin V double staining. Furthermore, decreased Bcl-2 accompanied by increased Bax (in western blotting) was found with TSL-1 treatment of H441 cells. TSL-1 treatment-induced G(1) arrest was concurrent with the down-regulation of protein levels of cyclin D1 and cyclin-dependent kinase 4 in H441 cells. Peroral and intraperitoneal administrations of TSL-1 were performed to evaluate the therapeutic efficacy, and peroral administration of TSL-1 was also used to elucidate the therapeutic efficacy in the H441 cell xenograft model in vivo. The data revealed that TSL-1 treatment inhibited H441 tumor growth in both therapeutic and preventive experiments. Taken together, these results demonstrate that TSL-1 possesses the capability of preventing and alleviating lung cancer proliferation in vitro and in vivo with proven nephrological and hepatic safety and has the potential to be developed as an anti-lung cancer drug.
Insights
Toona sinensis leaf extract TSL-1 shows significant antiproliferative effects against lung adenocarcinoma cells. This natural compound effectively inhibits tumor growth in vitro and in vivo, indicating potential as an anti-lung cancer drug.
Area of Science:
- Pharmacology
- Oncology
- Traditional Chinese Medicine
Background:
- Toona sinensis (T. sinensis) is a traditional Chinese herb with documented biological activities.
- Extracts from T. sinensis leaves exhibit diverse medicinal properties.
- Lung adenocarcinoma is a significant global health concern requiring novel therapeutic strategies.
Purpose of the Study:
- To investigate the antiproliferative effects of TSL-1, a bioactive fraction from T. sinensis leaf, on H441 lung adenocarcinoma cells.
- To elucidate the mechanisms underlying TSL-1's anti-cancer activity.
- To evaluate the in vivo therapeutic efficacy and safety of TSL-1 in a lung cancer model.
Main Methods:
- Antiproliferative activity was assessed using the MTT assay.
- Apoptosis induction was confirmed through cell morphology, sub-G1 DNA content analysis, PARP cleavage assays, and Annexin V/PI staining.
- Western blotting was employed to analyze the expression of apoptosis-related proteins (Bcl-2, Bax) and cell cycle regulators (cyclin D1, CDK4).
- In vivo efficacy was evaluated in a H441 cell xenograft mouse model using both therapeutic and preventive administration routes (peroral and intraperitoneal).
Main Results:
- TSL-1 demonstrated significant antiproliferative effects on H441 cells.
- TSL-1 induced apoptosis and G1 cell cycle arrest in H441 cells.
- Treatment with TSL-1 modulated the expression of Bcl-2 and Bax, and down-regulated cyclin D1 and CDK4.
- TSL-1 administration inhibited H441 tumor growth in vivo in both therapeutic and preventive settings.
- TSL-1 exhibited proven hepatic and renal safety.
Conclusions:
- TSL-1 exhibits potent in vitro and in vivo anti-lung cancer properties by inducing apoptosis and cell cycle arrest.
- TSL-1 demonstrates potential as a therapeutic agent for lung cancer, with demonstrated efficacy and safety.
- Further development of TSL-1 as a novel anti-lung cancer drug is warranted.