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• This article first discovered that CAR can inhibit the growth of osteosarcoma. • In this article, while studying the effect of CAR on osteosarcoma, it also studies its toxic and side effects on normal cells. • This article also studies the role of CAR in vitro and in vivo. • This study confirmed the mechanism of CAR inhibiting osteosarcoma through P 38 and JNK signaling pathway inhibitors. Osteosarcoma (OS) is the most common type of bone malignant tumors. Clinical commonly used therapeutic drugs of OS treatment are prone to toxic and side effects, so it is very urgent to develop new drugs with low toxicity and low side effects. As a Chinese herbal medicine, Cardamonin (CAR) (C 16 H 14 O 4) has inhibitory effects in various tumors. In the present study, we investigated the effects of CAR on OS cells in vitro and in vivo. We found that CAR inhibited cell proliferation, reduced migration, decreased invasion, and induced G2 / M arrest of OS cells. Notably, we demonstrated that CAR had no obvious effect on proliferation and apoptosis of normal cells. Besides, CAR repressed tumor growth of OS cells in xenograft mouse model. Mechanically, we found that CAR increased the phosphorylation level of P38 and JNK. In summary, our research validates that CAR may inhibit the proliferation, migration, and invasion of OS and promote apoptosis possibly by activating P38 and JNK Mitogen-activated protein kinase (MAPK) signaling pathway. [ABSTRACT FROM AUTHOR]