The molecular mechanisms of Caulophyllum robustum Maxim extract inhibition by regulating FAK/PI3K signaling pathway in gastric cancer HGC-27 cells

• Published in: Journal of ethnopharmacology 2025-01, Vol.337 (Pt 2), p.118867, Article 118867
• Main Authors: Cui, Minghua, Yao, Guangyuan, Zhang, Yingying, Wen, Meixin, Zhang, Shengjun, Jin, Jingchun, Lin, Zhenhua, Ren, Xiangshan, An, Renbo, Piao, Yingshi
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Caulophyllum robustum Maxim; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; FAK; Focal Adhesion Kinase 1 - metabolism; Gastric cancer; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Phosphatidylinositol 3-Kinases - metabolism; PI3K/AKT signaling pathway; Plant Extracts - pharmacology; Signal Transduction - drug effects; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Xenograft Model Antitumor Assays
• ISSN: 0378-8741; 1872-7573; 1872-7573
• DOI: 10.1016/j.jep.2024.118867

Caulophyllumrobustum Maxim extract (CRME), as recorded in traditional Chinese medicine, has the function of dispelling Feng, regulating Qi and dredging collaterals, promoting blood circulation and regulating menstruation, gingering up and relieving pain, clearing heat simultaneously detoxifying, lowering blood pressure and hemostasis. CRME is often used as Chinese materia medica preparation for rheumatoid arthritis, traumatic injury, irregular menstruation, abdominal pain, and hypertension treatment. Since gastric cancer (GC) existed as a health problem of human over the years, we are committed to the development of potential components of Chinese herbal medicine curing cancer, and we found CRME is expected to be one of the effective anti-tumor traditional Chinese medicine preparations. To investigate the molecular mechanisms of CRME anticancer effects and the potential links between CRME and FAK. Caulophyllumrobustum Maxim was extracted to obtain CRME, high-performance liquid chromatography (HPLC) was used for qualitative analysis. Information about CRME was collected from traditional Chinese medicine records and local surveys unpublished internationally. Series of cellular function experiments were applied to detect cell proliferation, migration, apoptosis, autophagy, cell cycle, angiogenesis. The xenograft model is employed in vivo. CRME can significantly inhibit HGC-27 cells on proliferation, migration and angiogenic capacity. Xenograft model indicated CRME inhibited cell proliferation in vivo. Annexin V-FITC/PI double staining assay and PI single staining assay depicted that CRME induces cell apoptosis, and arrests cell cycle at G0/G1 phase. AO (acridine orange) staining assay showed that CRME promoted autophagosome formation and inhibited autophagic flow. HPLC indicated Cauloside A and Cauloside C are components of CRME. Western blot indicated that FAK/PI3K signaling pathway is critical in the inhibition of CRME on HGC-27 cells. The anti-tumor components of CRME, Cauloside A and Cauloside C, inhibited tumor progression in HGC-27 cells. This inhibition is achieved by decreasing the phosphorylation levels of FAK, thereby modulating PI3K/AKT signaling pathway. [Display omitted] •Cauloside A and Cauloside C are the anti-tumor components of Caulophyllum Robustum Maxim Extract (CRME).•CRME inhibit EMT, apoptosis, cell cycle and angiogenesis in gastric cancer (GC) HGC-27 cells.•CRME decrease the phosphorylation levels of FAK.•FAK is involved in PI3K/AKT sig