-Repressed the survival, induced apoptosis and decreased the level of CD133, CD44, ABCG2, and ALDH1 mRNA in the spheres derived from U2OS and MG63 cells-Reduced the sphere formation rate of U2OS-SC and MG63-SC-Inhibited the tumor growth and reduced tumor size of U2OS-SC xenografts in nude mice-Reduced the DNMT1 activity and expression, increased miR-34a, and decreased Bcl-2 levels⇒ Isovitexin-mediated epigenetic regulation involves the DNMT1/miR-34a/Bcl-2 axis and causes the suppression of stemness and induction of apoptosis in the spheres derived from OS cells. Here, BCL2 is linked to neoplasm.