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.

中文翻译：

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DMAMCL在体外和体内均对肝细胞癌发挥抗肿瘤作用。

肝细胞癌（HCC）是一种常见的恶性肿瘤，预后较差。Dimethylaminomicheliolide（DMAMCL）是一种新型抗肿瘤药，已在I期临床试验中进行了测试；然而，对其在肝癌中的作用了解甚少。在这项研究中，我们发现DMAMCL以剂量和时间依赖性方式降低HCC细胞的活力。另外，DMAMCL导致细胞周期停滞在G2 / M期，并抑制细胞侵袭和上皮-间质转化（EMT）。DMAMCL处理还通过HCC细胞内在的凋亡途径诱导凋亡，这可能被泛半胱天冬酶抑制剂zVAD-fmk和Bax / Bak沉默或Bcl-2过表达所阻断。此外，DMAMCL处理会失活PI3K / Akt途径并导致活性氧（ROS）的产生，调节DMAMCL诱导的细胞凋亡并抑制PI3K / Akt。在体内，DMAMCL抑制携带异种移植HCC肿瘤的小鼠的肿瘤生长，而没有明显的毒性。总而言之，DMAMCL在体内和体外均具有抗肿瘤作用，因此可以用作HCC的潜在治疗剂。