Aims:
Peiminine has been reported to have various pharmacological properties, including anticancer activity. In this study, we investigated the effect of this
alkaloid on
osteosarcoma and explored the underlying mechanisms. Methods: To evaluate the antiosteosarcoma effects of
peiminine in vitro, cell viability was assessed by
CCK-8 and live/dead assays; the effects of the
drug on apoptosis and the cell cycle were examined by flow cytometry; the effects on cell migration and invasion were detected by wound healing and Transwell assays, respectively, while its effects on autophagy were observed by transmission electron microscopy and an LC3 fluorescent puncta formation assay. The role of autophagy in the
peiminine-mediated effects in
osteosarcoma cells was evaluated by
CCK-8 assay and western blotting after the application of the autophagy inhibitor
chloroquine. The effect of
peiminine on
reactive oxygen species (ROS) production was analyzed using fluorescence confocal microscopy and spectrophotometry. Additionally,
peiminine-treated
osteosarcoma cells were exposed to
SP600125, a JNK inhibitor, and
N-acetylcysteine, a ROS scavenger, after which the contribution of the ROS/JNK signaling pathway to
osteosarcoma was assessed using cell viability and LC3 fluorescent puncta formation assays, flow cytometry, and western blotting. A xenograft mouse model of
osteosarcoma was generated to determine the antitumor effects of
peiminine in vivo. Results:
Peiminine suppressed proliferation and
metastasis and induced cell cycle arrest, apoptosis, and autophagy in
osteosarcoma cells. These anticancer effects of
peiminine were found to be dependent on intracellular ROS generation and activation of the JNK pathway. In line with these results,
peiminine significantly inhibited xenograft
tumor growth in vivo. Conclusions:
Peiminine induced G0/G1-phase arrest, apoptosis, and autophagy in human
osteosarcoma cells via the ROS/JNK signaling pathway both in vitro and in vivo. Our study may provide an experimental basis for the evaluation of
peiminine as an alternative
drug for the treatment of
osteosarcoma.