Prunetin Triggers ROS-mediated Apoptosis through the Suppression of MAPKs/STAT-3/NF-κB-p65 Signaling Pathway in Human Osteosarcoma Cells

Osteosarcoma (OS) is a highly metastatic primary bone malignancy, and the treatment options remain inadequate. Hence, exploring innovative natural medications is required. Prunetin (PRU) is an isoflavone that has been a proven anticancer agent in numerous cancer cell lines. However, the activity of PRU against OS remains uncertain. Here, we studied the anticancer activity of PRU (20 and 25 µM) on human OS cells MG-63 and investigated its latent mechanism. The PRU activity of MG-63 cells cytotoxicity, intracellular ROS, metastasis, apoptosis, anti-apoptotic proteins, MAPK/STAT-3, and AKT signaling pathways was assessed by MTT assay, DCFH-DA, DAPI, PI, AO/EB, cell adhesion, and RT-PCR analysis. Findings unveiled that PRU could constrain MG-63 cell viability and adhesion through elevated intracellular ROS and elicited apoptosis. Likewise, PRU (20 and 25 µM) avert the MG-63 cell proliferation, which stimulates apoptosis by the enhancement of Bax and caspases, while it diminishes Bcl-2 in a dose-dependent way. Furthermore, PRU could reduce Pin-1, and anti-apoptotic elements, as well as trigger apoptotic signaling pathways. Our data established that PRU alleviates MG-63 cell proliferation and metastasis via ROS-mediated apoptosis, which triggers MAPKs/STAT3 and AKT pathways, suggesting that PRU is a promising natural remedy for OS. In order to comprehend the therapeutic target for cancer, we assessed the effect of PRU on the expression of Pin1, which is thought to be over-expressed in many human malignancies. According to our findings, PRU specifically suppressed Pin1 expression to reduce the expression of Akt, STAT3, P38, JNK, P65, and IL-6. We evaluated the impact of PRU on the expression of Pin1, which is allegedly over-expressed in many human malignancies, to better understand the therapeutic target for cancer. Researchers state that PRU inhibited the expression of Akt, STAT3, P38, JNK, P65, and IL-6 in particular, by suppressing Pin1 expression. Together, these results suggest that PRU may be an effective treatment for bone cancer in people by preventing Pin1 expression.