Polyphyllin VII induces mitochondrial apoptosis by regulating the PP2A/AKT/DRP1 signaling axis in human ovarian cancer.

Ovarian cancer is a gynecological malignancy with high mortality. Adjuvant therapy such as chemoradiotherapy inevitably leads to side effects and drug resistance. In recent years, traditional Chinese medicine has been widely studied for its safety, effectiveness, and unique pharmacological effects. Polyphyllin VII is an important component of Rhizoma paridis saponins, and has cytotoxic effects on many types of cancer cells. The aim of the present study was to evaluate the anti­tumor activity of polyphyllin VII in human ovarian cancer cells. Recent studies found that polyphyllin VII induces mitochondrial pathway apoptosis by increasing mitochondrial division, but the specific mechanism was unclear. The results of this study revealed that polyphyllin VII could effectively induce mitochondrial dysfunction, including increased mitochondrial division and reactive oxygen species (ROS) production. Notably, the mitochondrial location of dynamin­related protein 1 (DRP1) plays an important role in its function. In addition, polyphyllin VII enhanced the mitochondrial localization of DRP1 which is mediated by increased protein phosphatase 2A (PP2A) activity, and decreased AKT activity. A specific PP2A inhibitor, LB100, attenuated mitochondrial division and apoptosis in cells caused by polyphyllin VII, confirming the function of the PP2A/AKT pathway in polyphyllin VII treatment. Additionally, xenotransplantation experiments have also confirmed the anti­tumor effect of polyphyllin VII in vivo. Therefore, interference of the mitochondrial translocation of DRP1 through PP2A/AKT pathway may be an attractive and effective therapeutic approach by polyphyllin VII in ovarian cancer. This may provide new strategies for polyphyllin VII in the clinical treatment of ovarian cancer.

Development of 4,5-dihydro-benzodiazepinone derivatives as a new chemical series of BRD4 inhibitors.

Bromodomains (BRDs) are protein interaction modules that selectively recognize ε -N-lysine residues, serving as key epigenetic readers and play a key role in epigenetic regulation of gene transcription. Bromodomain-containing protein 4 (BRD4), a protein containing two BRDs termed BD1 and BD2, has emerged as an attractive candidate for the development of inhibitors targeting gene transcription in several types of cancers. In this study, we made structural modifications of previously reported BRD4 inhibitors, to develop new chemical scaffold 3,4-dihydroquinoxalin-2(1H)-one. Four series of compounds (compounds 7-10) were synthesized, and the BRD4-inhibitory activity and anti-proliferative effect of these compounds were evaluated. We found compound 10d has remarkable anti-proliferative activities toward leukemia cells and could induce apoptosis by mitochondrial pathways. Notably, the analysis of molecular docking suggested that hydrophobic interaction was essential for compound 10d to bind to BD1. In conclusion, these results demonstrate the potential of compound 10d to be utilized as a BRD4 inhibitor with apoptosis inducing effect in future leukemia therapy.

[Ultrasonic measurements of fetal thalamus, caudate nucleus and lenticular nucleus in prenatal diagnosis].

OBJECTIVE: To establish the reference values of thalamus, caudate nucleus and lenticular nucleus diameters through fetal thalamic transverse section. METHODS: A total of 265 fetuses at our hospital were randomly selected from November 2012 to August 2014. And the transverse and length diameters of thalamus, caudate nucleus and lenticular nucleus were measured. SPSS 19.0 statistical software was used to calculate the regression curve of fetal diameter changes and gestational weeks of pregnancy. P < 0.05 was considered as having statistical significance. RESULTS: The linear regression equation of fetal thalamic length diameter and gestational week was: Y = 0.051X+0.201, R = 0.876, linear regression equation of thalamic transverse diameter and fetal gestational week was: Y = 0.031X+0.229, R = 0.817, linear regression equation of fetal head of caudate nucleus length diameter and gestational age was: Y = 0.033X+0.101, R = 0.722, linear regression equation of fetal head of caudate nucleus transverse diameter and gestational week was: R = 0.025 - 0.046, R = 0.711, linear regression equation of fetal lentiform nucleus length diameter and gestational week was: Y = 0.046+0.229, R = 0.765, linear regression equation of fetal lentiform nucleus diameter and gestational week was: Y = 0.025 - 0.05, R = 0.772. CONCLUSIONS: Ultrasonic measurement of diameter of fetal thalamus caudate nucleus, and lenticular nucleus through thalamic transverse section is simple and convenient. And measurements increase with fetal gestational weeks and there is linear regression relationship between them.