Qingxuan Tong

Anti-proliferation and apoptosis induced by a novel intestinal metabolite of ginseng saponin in human hepatocellular carcinoma cells

20‐O‐(β‐d‐glucopyranosyl)‐20(S)‐protopanaxadiol (IH‐901), a novel intestinal bacterial metabolite of ginseng protopanaxadiol saponins, is reported to induce apoptosis in a variety of cancer cells. We purified the compound and measured its in vitro anti‐tumor activity. IH‐901 inhibited cell growth of human hepatocellular carcinoma SMMC7721 cells in a dose‐ and time‐dependent manner. We also found that IH‐901 induced apoptotic cell death concurrent with cell cycle arrest in G0–G1 phase in SMMC7721 cells. At the molecular level, we show that IH‐901 upregulates cytochrome c, p53, and Bax expression, and downregulates pro‐caspase‐3 and pro‐caspase‐9 expressions in a dose‐dependent manner, while the levels of Bcl‐2 and Bcl‐XL were unchanged in IH‐901‐treated SMMC7721 cells. These results provide significant insight into the anticarcinogenic action of IH‐901.

Ginsenoside Compound K Attenuates Metastatic Growth of Hepatocellular Carcinoma, which Is Associated with the Translocation of Nuclear Factor-κB p65 and Reduction of Matrix Metalloproteinase-2/9

The intestinal metabolite of ginseng saponin, compound K (CK), has various chemopreventive and chemotherapeutic activities, including anti-tumor activity. However, the functional mechanisms through which CK attenuates metastatic growth in hepatocellular carcinoma (HCC) remain unclear. Here, using multiple IN VITRO and IN VIVO models, we reported that CK strongly attenuated colony formation, adhesion, and invasion of HCC cells IN VITRO and dramatically inhibited spontaneous HCC metastatic growth IN VIVO. At the molecular level, immunofluorescence and Western blotting analysis confirmed that inhibition of metastatic growth of HCC induced by CK treatment caused a time-dependent decrease in nuclear NF- κB p65 and a concomitant increase in cytosolic NF- κB p65, indicating that CK suppressed the activation of the NF- κB pathway. Meanwhile, our study showed that the inhibition of matrix metalloproteinase2/9 (MMP2/9) expression caused by CK treatment was associated with NF- κB p65 nuclear export. Taken together, our results not only revealed that NF- κB p65 nuclear export and the reduction of MMP2/9 expression were associated with the metastatic inhibition induced by CK, but also suggested that CK may become a potential cytotoxic drug in the prevention and treatment of HCC.

Corilagin inhibits hepatocellular carcinoma cell proliferation by inducing G2/M phase arrest

Hepatocellular carcinoma (HCC) is one of most common types of malignant tumours. Therefore, it is very important to identify powerful drugs and their antitumour mechanisms. Corilagin has a significant antitumour potential and lower toxicity in normal cells in vitro. The IC50 values of corilagin for normal Chang‐liver cells and the HCC cell lines Bel7402 and SMMC7721 were 131.4, 24.5 and 23.4 µM, respectively, in the methyl thiazolyl tetrazolium (MTT) assay. MHCC97‐H xenografts in Balb/c mice intraperitoneally injected with 30 mg/kg corilagin for 5 weeks showed a 47.3% inhibition of tumour growth in vivo. Furthermore, data from flow cytometry and Western blot analyses of cell cycle and cell cycle‐related proteins suggest that corilagin arrests SMMC7721 cells at the G2/M phase by downregulating p‐Akt and cyclin B1/cdc2 and upregulating p‐p53 and p21Cip1. In conclusion, corilagin is a potential antitumour drug that is effective in retarding the growth of HCC, which is correlated with the activation of p‐p53‐p21Cip1‐cdc2/cyclin B1.

Corilagin induces the apoptosis of hepatocellular carcinoma cells through the mitochondrial apoptotic and death receptor pathways

Corilagin, a gallotannin, is one of the major active components of many ethnopharmacological plants and exhibits antitumor, anti-inflammatory and antioxidative properties. In recent years, corilagin has provoked much attention due to its antitumor activity, yet the mechanisms attributed to its anticancer actions are largely unknown. In our previous research, our group reported that corilagin could inhibit the proliferation of hepatocellular carcinoma (HCC) cells by inducing G2/M phase arrest. In the present study, observation of the morphological changes showed that corilagin induced the apoptosis of HCC cells as determined by AO/EB and Hoechst 33258 staining assays. Furthermore, flow cytometric analysis was carried out to calculate the apoptotic rate which was 24.1% following treatment with corilagin (37.5 µM). At the molecular level, mitochondrial membrane potential assay and western blot analysis showed that the mitochondrial transmembrane potential was reduced and the rate of release of cytochrome c was increased, which led to the activation of caspase-9, caspase-3 and cleavage of PARP in the cytoplasm indicating activation of the mitochondrial apoptotic pathway. Moreover, following treatment with corilagin, we noted upregulation of Fas and FasL and activation of caspase-8 which represented activation of the death receptor pathway, and we also observed downregulation of Bcl-2 and survivin which was also attributed to the antitumor effect of corilagin. These results suggest that corilagin significantly induced the apoptosis of HCC cells through both the mitochondrial apoptotic pathway and the death receptor pathway, and corilagin is a potential complementary anticancer herbal drug for HCC therapy.

High variability in the N terminus of coat protein among potyviruses and its advantage in producing a specific antibody

Cross reaction often occurs in serological detection for potyviruses that can lead to false positive results. Sequence alignment revealed that the N-terminal sequences of coat proteins (CP) are highly variable among potyviruses. Based on this finding, the preparation of a specific antibody against potyviruses is described here increasing the efficiency of detection and identification. A case study of Turnip mosaic virus (TuMV): a specific fragment “CP-50” (1–50 aa of CP) was obtained by prokaryotic expression and used for producing the polyclonal antibody. Test of specificity indicated that the prepared antibody “Anti-CP-50” strongly reacted with TuMV and is appropriate as a specific anti-TuMV antibody.

Corilagin, a promising medicinal herbal agent

Corilagin, a gallotannin, is one of the major active components of many ethnopharmacological plants. It was isolated from Caesalpinia coriaria (Jacq.) Willd. (dividivi) by Schmidt in 1951 for the first time. In the past few decades, corilagin was reported to exhibit anti-tumor, anti-inflammatory and hepatoprotective activities, etc. However, little attention was paid to its pharmacological properties due to the complicated and inefficient extract method. In recent years, with the development of extraction technology corilagin was much easier to obtain than before. Thus, people return to pay attention to its anti-tumor, hepatoprotective, and anti-inflammatory activities, particularly as an anti-tumor agent candidate. Our research team had focused on the distribution, preparation and anti-tumor activity of corilagin since 2005. We found corilagin showed good anti-tumor activity on hepatocellular carcinoma and ovarian cancer. Whats more, corilagin showed a low level of toxicity toward normal cells and tissues. Due to the extensive attention that corilagin has received, we present a systematic review of the pharmacological effects of corilagin. In this review, we summarized all the pharmacological effects of corilagin with a focus on the molecular mechanism of anti-tumor activity and show you how corilagin affected the signaling pathways of tumor cells as well as its physicochemical properties, distribution and preparation methods.