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DMAMCL exerts antitumor effects on hepatocellular carcinoma both in vitro and in vivo.

Cancer letters (2020-04-09)
Shunnan Yao, Jianpin Ye, Mengqi Yin, Rui Yu
RESUMEN

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. Dimethylaminomicheliolide (DMAMCL) is a novel antitumor agent that has been tested in phase I clinical trials; however, little is known regarding its effects in HCC. In this study, we found that DMAMCL reduces the viability of HCC cells in a dose- and time-dependent manner. In addition, DMAMCL causes cell cycle arrest at the G2/M phase and inhibits cell invasion and epithelial-mesenchymal transition (EMT). DMAMCL treatment also induces apoptosis via the intrinsic apoptotic pathway in HCC cells, which could be blocked by the pan-caspase inhibitor zVAD-fmk and silencing of Bax/Bak or overexpression of Bcl-2. Furthermore, DMAMCL treatment inactivates the PI3K/Akt pathway and leads to the generation of reactive oxygen species (ROS), which regulate apoptosis and inhibition of PI3K/Akt induced by DMAMCL. In vivo, DMAMCL inhibits tumor growth in mice bearing xenograft HCC tumors without noticeable toxicity. In summary, DMAMCL exerts antitumor effects both in vitro and in vivo and therefore may be applied as a potential therapeutic agent for HCC.

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