Shikonin, a natural naphthoquinone, induces necroptosis in various cancer cell lines such as glioma, osteosarcoma, and hematopoietic cells by enhancing RIP1 and RIP3 and mROS, and also effectively overcomes P-gp, Bcl-2, Bcl-xl, MRP1, and BCRP1 drug resistance [37]. Here, BCL2 is linked to osteosarcoma.