In this study, we reported millepachine (MIL), a novel chalcone compound for the first time isolated from Millettia pachycarpa Benth (Leguminosae), induced cell cycle arrest and apoptosis in human hepatocarcinoma cells in vitro and in vivo . In in vitro screening experiments, MIL showed strong antiproliferation activity in several human cancer cell lines, especially in HepG2 cells with an IC ₅₀ of 1.51 µM. Therefore, we chose HepG2 and SK-HEP-1 cells to study MIL’s antitumor mechanism. Flow cytometry showed that MIL induced a G ₂ /M arrest and apoptosis in a dose-dependent manner. Western blot demonstrated that MIL-induced G ₂ /M arrest was correlated with the inhibition of cyclin-dependent kinase 1 activity, including a remarkable decrease in cell division cycle (cdc) 2 synthesis, the accumulation of phosphorylated-Thr14 and decrease of phosphorylation at Thr161 of cdc2. This effect was associated with the downregulation of cdc25C and upmodulation of checkpoint kinase 2 in response to DNA damage. MIL also activated caspase 9 and caspase 3, and significantly increased the ratio of Bax/Bcl-2 and stimulated the release of cytochrome c into cytosol, suggesting MIL induced apoptosis via mitochondrial apoptotic pathway. Associated with those effects, MIL also induced the generation of reactive oxygen species. In HepG2 tumor-bearing mice models, MIL remarkably and dose dependently inhibited tumor growth. Treatment of mice with MIL (20mg/kg intravenous [i.v.]) caused more than 65% tumor inhibition without cardiac damage compared with 47.57% tumor reduction by 5mg/kg i.v. doxorubicin with significant cardiac damage. These effects suggested that MIL and its easily modified structural derivative might be a potential lead compound for antitumor drug.

The purpose of this review is to elaborate the role of Periplaneta (P.) americana L. in modern and traditional Chinese medicine (TCM) and compare the use of the species in these two forms of medical treatments. From searches on Google Scholar, PubMed, and Web of Science databases, studies were identified involving TCMs with P. americana, which have a history of use over several thousand years, and demonstrate how extracts from this insect play a role in the treatment of diseases through antibacterial, antiviral, antitumor activity, and enhancement of immune function. Extracts from P. americana have not been fully developed for clinical use because the active components have not been completely purified or their molecular mechanisms thoroughly understood. The development of extraction technology in modern Chinese medicine has revealed that many extracts from P. americana are able to play an important role in the control of diseases such as cancer. Drugs such as ‘Kangfuxin Solution’ and ‘Xinmailong Injection’ are now widely used for gastrointestinal ulcers and chronic heart failure, having achieved beneficial curative effects in clinical studies. Based on this, the information from studies of P. americana in TCM and modern medicine should be combined and their respective advantages applied. This review provides an overview of the role of P. americana in modern and TCM and thus contributes to identification of further applications and area requiring drug development.