Tankyrase (TNKS) plays important roles in the malignancy of several cancers such as human lung tumor, breast cancer, and hepatocellular cancer. However, its exact functions and molecular mechanisms in ovarian cancer remain unclear. In this study, we found that TNKS was aberrantly overexpressed in human ovarian cancer tissues and associated with poor patient prognosis. TNKS inhibition or knockdown not only reduced ovarian cancer cell proliferation, colony formation, migration, invasion, and tumorigenic potential in nude mice but also enhanced the drug susceptibility of ovarian cancer cells through arresting cell cycle and inducing apoptosis. These phenotypic changes correlated with downregulation of targets (Cyclin D1, MDR, and MMP-9) of Wnt/β-catenin signaling. Furthermore, downregulation of TNKS suppressed the glucose uptake, lactate excretion, and cellular ATP levels and increased cellular O2 consumption rates. Molecular mechanism studies revealed that TNKS promoted aerobic glycolysis at least in part due to upregulation of pyruvate carboxylase (PC) via activation of Wnt/β-catenin/snail signaling. In agreement with these findings, expression of TNKS is positively associated with snail and PC in clinical ovarian cancer samples. Our findings identified TNKS as an oncogenic regulator of ovarian cancer cells proliferation that promotes aerobic glycolysis via activation of Wnt/β-catenin signaling, indicating that the TNKS might serve as a potential molecular target for clinical therapy of Wnt/β-catenin dependent ovarian cancer.

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The flavonoids in Ageratum conyzoides L. have been used in traditional medicine due to its anti-inflammatory and antibacterial properties. However, the specific mechanism of its antibacterial effect, and the potential therapeutic effect on vaginitis have not been well explained. The growth curves of E. coli, S. aurues, and P. aeruginosa after treatment with flavonoids were measured. The influences of flavonoids on the conductivity of bacterial culture medium and exudation of bacterial nucleic acid were also detected. Transcriptomics analysis was applied to analyze the potential mechanism of flavonoids. Flavonoids significantly suppressed the growth curves of E. coli, S. aurues, and P. aeruginosa, and increased the conductivity of bacteria and nucleic acid exudation. Transcriptomics analysis indicated that flavonoids could suppress bacteria by affecting the transcription and metabolism pathways. The obvious therapeutic effect of flavonoids on bacterial vaginitis was also observed. This study systematically analyzed the bacteriostatic mechanism of flavonoids, which should be helpful to develop new drugs based on the bacteriostatic effect of flavonoids.

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PurposeDiosgenin (DSG) is the precursor of steroid hormones and plays a crucial part in the proliferation of various carcinomas including human colorectal cancer and gastric carcinoma. Nevertheless, its specific features and mechanisms in human cholangiocarcinoma (CCA) remain unknown.MethodsMTS assay, colony-forming assay, and EdU assay were performed to determine the role of DSG on the progression of human CCA cells. The distributions of cell cycle, the ratio of apoptosis, and the mitochondrial membrane potential (ΔΨm) were studied by flow cytometry (FCM). AO/EB and Hoechst 33258 staining were performed to observe the morphological features of cell apoptosis. TEM was performed to observe the ultrastructures of QBC939 and HuCCT1 cells. The mRNA and protein expression of mitochondrial apoptotic pathway and GSK3β/β-catenin pathway were further confirmed by qPCR and Western blotting. The xenograft tumor model of HuCCT1 cells was built. Immunohistochemistry of tumor tissues was performed.ResultsOur results indicated that DSG inhibited the progression of six CCA cell lines. In vivo tumor studies also indicated that DSG significantly inhibited tumor growth in xenografts in nude mice. The expression of mitosis-promoting factor cyclinB1 was decreased along with the elevating level of cell cycle inhibitor p21, resulting in arresting CCA cell cycles at G2/M phase. Furthermore, DSG induced apoptosis with the increased expressions of cytosol cytochrome C, cleaved-caspase-3, cleaved-PARP1 and the Bax/Bcl-2 ratio. Mechanistically, our study showed that GSK3β/β-catenin pathway was involved in the apoptosis of CCA cells. Thus, DSG might provide a new clue for the drug therapy of CCA.ConclusionIn our data, DSG was found to have efficient antitumor potential of human CCA cells in vitro and in vivo.

The Ageratum conyzoides L. (A. conyzoides) is commonly used as a traditional medicine, and its antitumor effects have also been studied. However, the functional roles of flavonoids in A. conyzoides in antitumor activities have not been clarified. The present study is aimed at investigating the biological effects of flavonoids in A. conyzoides on human cervical adenocarcinoma. Firstly, we detected that flavonoids in A. conyzoides significantly inhibited the proliferation, invasion, migration, and clonality of human cervical adenocarcinoma HeLa cells in vitro. Furthermore, we found that flavonoids in A. conyzoides induced significant S phase arrest and apoptosis and obviously decreased the intracellular reactive oxygen species (ROS) level in HeLa cells. Finally, we found that flavonoids in A. conyzoides significantly inhibited the HeLa xenograft tumor growth and epithelial-mesenchymal transition (EMT) in vivo. In conclusion, our results demonstrated the obvious antitumor effects of flavonoids in A. conyzoides on HeLa cells, suggesting that flavonoids in A. conyzoides could be provided as a novel therapeutic compound for human cervical adenocarcinoma.

Our results demonstrated that RARα knockdown suppressed the tumorigenicity of EC via Wnt/β-catenin pathway. RARα might be a potential molecular target for EC clinical therapy.

Abnormal expression and function of retinoic acid receptor α (RARα) have been reported to be associated with various cancers including acute promyelocytic leukemia and hepatocellular carcinoma. However, the role and the mechanism of RARα in gastric carcinoma (GC) were unknown. Here, the expression of RARα was frequently elevated in human GC tissues and cell lines, and its overexpression was closely correlated with tumor size, lymph node metastasis and clinical stages in GC patients. Moreover, RARα overexpression was related with pathological differentiation. Functionally, RARα knockdown inhibited the proliferation and metastasis of GC cells, as well as enhanced drug susceptibility both in vitro and in vivo. Additionally, RARα knockdown suppressed GC progression through regulating the expression of cell proliferation, cell cycle, invasion and drug resistance associated proteins, such as PCNA, CyclinB1, CyclinD2, CyclinE, p21, MMP9 and MDR1. Mechanistically, the above oncogenic properties of RARα in GC were closely associated with Akt signaling activation. Moreover, overexpression of RARα was induced by IL-1β/Akt signaling activation, which suggested a positive feedback loop of IL-1β/Akt/RARα/Akt signaling in GC. Taken together, we demonstrated that RARα was frequently elevated in GC and exerted oncogenic properties. It might be a potential molecular target for GC treatment.