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Luteolin enhances TNF-related apoptosis-inducing ligand's anticancer activity in a lung cancer xenograft mouse model
Jiaqi Yan1, Qiong Wang, Xuelian Zheng
1Laboratory of Molecular and Translational Medicine, Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Abstract:
Sensitization of cancer cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by luteolin has been suggested by in vitro studies. However, no in vivo experiment has been reported to validate the potentiation effect of luteolin on TRAIL's anticancer activity. In this report, we first confirmed that luteolin potentiates TRAIL-induced cytotoxicity in A549 cells and HeLa cells in association with increased activation of apoptosis. Then we performed an in vivo experiment with a non-small cell lung cancer xenograft mouse model, which showed for the first time that the in vivo anticancer activity of TRAIL was greatly enhanced by luteolin. Compared with that in untreated control or treatment with TRAIL or luteolin alone, inhibition of tumor growth and apoptotic cell death in xenograft tumors were significantly increased in animals receiving combination treatment with TRAIL and luteolin. Data from this study thus provide strong in vivo evidence supporting that luteolin is a potential sensitizer for TRAIL in anticancer therapy.
Insights
Luteolin enhances the anticancer effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in preclinical models. This study provides the first in vivo evidence that luteolin sensitizes cancer cells to TRAIL therapy, improving tumor growth inhibition.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- In vitro studies suggest luteolin can sensitize cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis.
- Previous research lacked in vivo validation of luteolin's potentiating effect on TRAIL's anticancer activity.
Purpose of the Study:
- To investigate the in vivo efficacy of luteolin as a sensitizer for TRAIL-based anticancer therapy.
- To validate the potentiation of TRAIL's anticancer activity by luteolin in a preclinical cancer model.
Main Methods:
- Confirmed luteolin's potentiation of TRAIL-induced cytotoxicity and apoptosis in A549 and HeLa cancer cell lines in vitro.
- Utilized a non-small cell lung cancer xenograft mouse model for in vivo experiments.
Main Results:
- Luteolin significantly enhanced TRAIL-induced cytotoxicity and apoptosis in vitro.
- In vivo, combination treatment with TRAIL and luteolin markedly inhibited tumor growth compared to single-agent treatments or controls.
- Increased apoptotic cell death was observed in xenograft tumors from the combination therapy group.
Conclusions:
- Luteolin acts as an effective in vivo sensitizer for TRAIL in anticancer therapy.
- This study provides strong preclinical evidence supporting the combined use of luteolin and TRAIL for cancer treatment.
