MAPK8 and cancer: In conclusion, the combined treatment of PL with ZA suppressed the formation of cancer-induced osteoclastogenesis and tumorigenesis synergistically both in vitro and in vivo. Synergistic treatment with PL and ZA attenuated RANKL-stimulated activation of NF-κB and MAPK signaling pathways during osteoclast formation through structural simulation of ANP to target competitively phosphorylation of JNK/Erk.