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Decrease in GPSM2 mediated by the natural product luteolin contributes to colon adenocarcinoma treatment and
Chunjiao Yang1, Lina Wu2, Xin Jin3
1The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, China; Department of Oncology, The Fifth Affiliated Hospital of Guangxi Medical University & The First People's Hospital of Nanning, Nanning, Guangxi, China.
Summary
Luteolin and Brucea javanica oil emulsion injection (BJOEI) fight colon cancer by targeting GPSM2 and the FoxO pathway. This discovery offers a new therapeutic strategy for colon adenocarcinoma (COAD).
Area of Science:
- Natural Product Chemistry
- Molecular Biology
- Oncology
Background:
- Luteolin, a natural compound from Brucea javanica (BJ), and BJ oil emulsion injection (BJOEI) show anti-tumor potential.
- The precise molecular mechanisms underlying their anti-cancer effects, particularly in colon adenocarcinoma (COAD), remain unclear.
Purpose of the Study:
- To elucidate the molecular mechanism of luteolin and BJOEI in treating COAD.
- To investigate the role of GPSM2 and the FoxO signaling pathway in mediating these anti-cancer effects.
Main Methods:
- Molecular docking simulations to predict interactions between luteolin and GPSM2.
- In vitro experiments involving knockdown and overexpression of GPSM2 in COAD cells.
- In vivo studies using RKO and SW480 xenograft mouse models.
- Verification of BJOEI's effects in combination with fluorouracil.
Main Results:
- Luteolin directly interacts with GPSM2, regulating the FoxO signaling pathway.
- GPSM2 is essential for luteolin's anti-proliferative effects on COAD cells; its knockdown offsets inhibition, while overexpression reverses it.
- BJOEI inhibits COAD progression via GPSM2 and the FoxO pathway, with enhanced efficacy when combined with fluorouracil.
Conclusions:
- The anti-tumor effects of luteolin and BJOEI on COAD are dependent on GPSM2.
- Targeting GPSM2 to modulate the FoxO signaling pathway presents a promising therapeutic approach for COAD treatment.
