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[Display omitted] • Acacetin weakens the proliferation, migration and invasion of osteosarcoma cells. • Acacetin promotes the apoptosis of osteosarcoma cells. • Xenograft mouse osteosarcoma model confirms the inhibitory effect in vivo. • The signal pathway is predicted by network pharmacology and confirmed by the experiments. Osteosarcoma (OS) is the most common primary malignant bone tumor with high lung metastasis and mortality rate. Neo-adjuvant chemotherapy combined with limb salvage is the main treatment strategy for OS. However, because of the tolerance to conventional chemotherapy and the cell toxicity of chemotherapy drugs, new drugs with lower toxicity for OS are urgently needed. Acacetin is a natural flavonoid compound that has inhibitory effects on many kinds of tumors. Herein, we explored the impact of acacetin on OS cell growth in vitro and in vivo. We discovered that acacetin suppressed the proliferation, migration and invasion, while promoted the apoptosis of OS cells. Notably, acacetin had little impact on proliferation and apoptosis of human normal cells. Furthermore, we confirmed that acacetin repressed the growth and metastasis of OS in xenograft mouse model in vivo. Mechanically, we discovered that acacetin activated JNK pathway and inactivated Wnt/β-catenin pathway. β-catenin over-expression or JNK inhibitor SP600125 was able to partially neutralize acacetin-induced inhibitory effect on OS cells. To sum up, our study implies that acacetin may inhibit tumor growth of human OS cells through regulating Wnt/β-catenin and JNK signaling pathways. [ABSTRACT FROM AUTHOR]

• 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]

Osteosarcoma (OS) is an aggressive malignant skeletal tumor characterized by an extremely poor prognosis and a high tendency to recur. The frequently used anti-OS chemotherapy regents are often limited by drug resistance and severe adverse events. It is urgent to develop more effective, tolerable and safe drugs for the treatment of OS. Andrographolide (AG), a diterpenoid lactone isolated from Andrographis paniculata, has been proved to possess anti-tumor activity against several human cancer types. In this current study, we evaluated the inhibitory effect of AG on human OS cells and probed the possible mechanism. We found that AG inhibited the proliferation of human OS cells and blocked cell cycle at G2/M phase. Furthermore, AG impeded the migration and invasion, while promoted the apoptosis of human OS cells. Moreover, we found that AG inhibited OS growth and lung metastasis in orthotopic transplantation model. Mechanistically, we demonstrated that AG suppressed the activity of Wnt/β-catenin, PI3K/AKT and NF-κB signaling pathways. Notably, we validated that AG synergized with the inhibitors of Wnt/β-catenin, PI3K/AKT and NF-κB to suppress the proliferation, migration and invasion of human OS cells. Collectively, our study conclusively demonstrates that AG inhibits the growth of human OS cells, thus, may be a promising candidate for the treatment of OS. • Andrographolide effectively inhibited osteosarcoma cell growth in vitro and in vivo. • Andrographolide had relative lower toxicity against normal cells. • Andrographolide suppressed Wnt/β-catenin, PI3K/AKT and NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]