Decrease in GPSM2 mediated by the natural product luteolin contributes to colon adenocarcinoma treatment and increases the sensitivity to fluorouracil

• Published in: Biomedicine & pharmacotherapy Vol. 176; p. 116847
• Main Authors: Yang, Chunjiao, Wu, Lina, Jin, Xin, Liu, Aoran, Jing, Zhitao, Feng, Chuhan, Guo, Zhengting, Zhang, Yuzhe, Ma, Yanju, Li, Fang, Wen, Zhenpeng, Yan, Lirong, Yang, Yi, Ji, Xu, Zhang, Ye
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.07.2024; Elsevier
• Subjects: Brucea javanica oil emulsion injection (BJOEI); Colon adenocarcinoma (COAD); FoxO signaling pathway; G-protein-signal modulator 2 (GPSM2); Luteolin; FoxO signaling pathway; Luteolin; G-protein-signal modulator 2 (GPSM2); Colon adenocarcinoma (COAD); Brucea javanica oil emulsion injection (BJOEI)
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.116847

Luteolin, a monomeric substance, is a natural product of the Brucea javanica (BJ) plant. Brucea javanica oil emulsion injection (BJOEI) is a proprietary Chinese medicine purified from BJ that is widely used clinically as an anti-tumor treatment. Although a growing body of research suggests that luteolin and BJOEI have anti-tumor effects, the molecular mechanism of action has not been fully elucidated. In this study, through molecular docking technology, we found that luteolin can interact directly with GPSM2 and regulate the FoxO signaling pathway through GPSM2. In addition, the inhibitory effect of luteolin on colon adenocarcinoma (COAD) cells was found to be offset by knockdown of GPSM2. In contrast, the anti-proliferative effects of luteolin could be notably reversed by overexpression of GPSM2. The results reveal that GPSM2 is crucial in luteolin-mediated anti-proliferative effects. The mediation of anti-proliferative effects by GPSM2 has also been indirectly demonstrated in RKO and SW480 xenograft mice models. In addition, we verified that BJOEI inhibits the progression of COAD by mediating GPSM2 and regulating the FoxO signaling pathway. We also found that BJOEI achieved a better anti-tumor effect when combined with fluorouracil injection. Collectively, our data show that the anti-tumor effects of BJOEI and luteolin on COAD are GPSM2-dependent and downregulating the expression of GPSM2 to regulate the FoxO signaling pathway may be an effective way to treat COAD. [Display omitted] •Luteolin is a natural product of the Brucea javanica monomeric component that is widely used in antitumour treatment.•Luteolin and Brucea javanica oil emulsion injection can inhibit colon cancer progression.•The anticancer mechanism of luteolinrevealed and laid a solid foundation for its clinical application.