2. Academic Validation
  3. Decrease in GPSM2 mediated by the natural product luteolin contributes to colon adenocarcinoma treatment and increases the sensitivity to fluorouracil

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

  • Biomed Pharmacother. 2024 Jul:176:116847. doi: 10.1016/j.biopha.2024.116847.
Chunjiao Yang 1,  Lina Wu 2,  Xin Jin 3,  Aoran Liu 4,  Zhitao Jing 5,  Chuhan Feng 6,  Zhengting Guo 7,  Yuzhe Zhang 4,  Yanju Ma 8,  Fang Li 4,  Zhenpeng Wen 9,  Lirong Yan 4,  Yi Yang 10,  Xu Ji 11,  Ye Zhang 12
Affiliations

Affiliations

  • 1 The 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.
  • 2 Department of Laboratory Medicine, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, Liaoning 110004, China; Liaoning Clinical Research Center for Laboratory Medicine, Shenyang, China.
  • 3 Department of Respiratory Medicine, The Fifth Affiliated Hospital of Guangxi Medical University & The First People's Hospital of Nanning, Nanning, Guangxi, China.
  • 4 The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, China.
  • 5 The First Hospital of China Medical University, Shenyang, China.
  • 6 Liaoning University Of Traditional Chinese Medicine, Shenyang, China.
  • 7 The First Clinical College, China Medical University, Shenyang, China.
  • 8 Department of Medical Oncology, Cancer Hospital of China Medical University, China.
  • 9 The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, China; Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • 10 Department of Laboratory Animal Science, China Medical University, Shenyang, China.
  • 11 The First Hospital of China Medical University, Shenyang, China. Electronic address: cmujixu@163.com.
  • 12 The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, China. Electronic address: zhangyecmu@163.com.
PMID: 38823277 DOI: 10.1016/j.biopha.2024.116847
Abstract

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.

Keywords

Brucea javanica oil emulsion injection (BJOEI); Colon adenocarcinoma (COAD); FoxO signaling pathway; G-protein-signal modulator 2 (GPSM2); Luteolin.

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