Moreover, our study also revealed that diosmetin downregulated anti-apoptotic protein Bcl-xL while upregulated pro-apoptotic proteins such as cleaved Caspase-3, cleaved-PARP and Bax in osteosarcoma Saos-2 and U2SO cells, together with the suppression of p-STAT3 and c-Myc, suggesting that STAT3/c-Myc signaling pathway might be involved in the anti-proliferative and pro-apoptotic effects of diosmetin. Here, CASP3 is linked to osteosarcoma.