Norcantharidin inhibits proliferation and promotes apoptosis via c‐Met/Akt/mTOR pathway in human osteosarcoma cells

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor and frequently affects adolescents. Norcantharidin (NCTD), a demethylated derivative of cantharidin, has been reported to exhibit anticancer activity against various types of tumors but not human OS. The aim of the present study was to evaluate the effects of NCTD on OS cell lines (MG63 and HOS) and to explore the underlying mechanisms. In the present study, the proliferation of OS cells decreased significantly, while the apoptosis was accelerated significantly after exposure to NCTD. Meanwhile, our results also indicated that NCTD could suppress the migration and invasion, decrease the colony‐forming ability and induce S phase cell cycle arrest of OS cells in a dose‐dependent manner. Moreover, our results revealed that the anticancer effects induced by NCTD on OS cells involved autophagy, mitophagy, endoplasmic reticulum stress and c‐Met pathway. Furthermore, the results of animal experiments showed that NCTD inhibited tumor growth in a xenograft model of human OS. These results provide important new insight into the possible molecular mechanisms of NCTD and highlight its potential use as an antitumor drug for human OS.

Strontium/Chitosan/Hydroxyapatite/Norcantharidin Composite That Inhibits Osteosarcoma and Promotes Osteogenesis In Vitro

“…By evaluating the effects of NCTD on OS cell lines (MG63 and HOS) in vitro and in vivo, we found that NCTD can inhibit cell cycle and induce apoptosis of human OS cells. ese effects are mediated by autophagy induction, triggering ER stress and inactivation of the c-Met/ Akt/mTOR pathway [23]. It works when the proliferation and apoptosis of normal cells are out of balance by inhibiting and then inducing apoptosis of tumor cells [24].…”

FAM64A Promotes Osteosarcoma Cell Growth and Metastasis and Is Mediated by miR-493

“…However, the research of FAM64A is inadequate; thus, the role of FAM64A in OS cells is still poorly understood. e dysregulation of intracellular signaling pathways such as Notch1, Akt, Wnt pathway, and JAK2/STAT3 was reported to be participated in the development of OS [3][4][5][6]. Xu et al found that FAM64A served as a positive regulator of STAT3, which is linked to various cancer types [7].…”

Cantharidic acid induces apoptosis in human nasopharyngeal carcinoma cells through p38‐mediated upregulation of caspase activation

“…These side effects are mainly because the therapies not only damage cancer cells, but also normal cells in the body . On the other hand, previous studies have suggested that cantharidin is not cytotoxic to normal cells both in vitro and in vivo . Furthermore, several studies have indicated that cantharidin induces apoptosis in various human cancer cells such as human leukemic cells and human hepatocellular carcinoma cells .…”