Genipin promotes the apoptosis and autophagy of neuroblastoma cells by suppressing the PI3K/AKT/mTOR pathway

• Published in: Scientific reports Vol. 14; no. 1; pp. 20231 - 20
• Main Authors: Liu, Xinying, Zhou, Can, Cheng, Boli, Xiong, Yan, Zhou, Qin, Wan, Enyu, He, Yun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/67; 631/67/1059; 631/67/1059/153; 631/67/2332; AKT protein; Animals; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Cancer therapies; Caspase-3; Cell Line, Tumor; Cell Survival - drug effects; Cell viability; Cytotoxicity; Drug resistance; Flow cytometry; Genipin; Humanities and Social Sciences; Humans; Immunofluorescence; Iridoids - pharmacology; Kinases; Medical prognosis; Medical schools; Metabolism; Mice; multidisciplinary; Natural products; Neuroblastoma; Neuroblastoma - drug therapy; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neuroblasts; Pediatrics; Phosphatidylinositol 3-Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Radiation; Science; Science (multidisciplinary); Signal transduction; Signal Transduction - drug effects; TOR protein; TOR Serine-Threonine Kinases - metabolism; Tumors; Western blotting; Xenograft Model Antitumor Assays
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-71123-w

This study investigated the underlying function and mechanism of genipin in neuroblastoma (NB). Using flow cytometry analysis and cytotoxicity tests, in vitro studies were conducted to assess the effects of genipin on the SK-N-SH cell line. The mechanism of action of genipin was explored through immunofluorescence staining, Western blotting, and caspase-3 activity assays. In addition, we also created a xenograft tumour model to investigate the effects of genipin in vivo. This research confirmed that genipin suppressed cell viability, induced apoptosis, and promoted autophagy, processes that are likely linked to the inhibition of the PI3K/AKT/mTOR signalling pathway. Autophagy inhibition increases the sensitivity of SK-N-SH cells to genipin. Furthermore, combination treatment with a PI3K inhibitor enhanced the therapeutic efficacy of genipin. These results highlight the potential of genipin as a candidate drug for the treatment of NB.