Pterostilbene inhibits MTA1/HDAC1 complex leading to PTEN acetylation in hepatocellular carcinoma.

PURPOSE: The aim of this study is to investigate the inhibition of cancer growth by pterostilbene through Metastasis-Associated Protein 1 (MTA1) and the histone deacetylase 1 (HDAC1) complex in hepatocellular carcinoma (HCC). METHODS: We investigate the antitumor effects of pterostilbene (PTER) in HCC. The SMMC-7721 hepatoma cell line was cultured and treated with PTER for different time depending on the experiment. After treatment, we tested the cellular expression of proteins by Western blot and the expression of MTA1 mRNA by real-time PCR. And the immunoprecipitation was performed to confirm the acetylation in PTEN. Animal models have been established to confirm the anti-cancer effects of PTER. RESULTS: PTER treatment could downregulate the expression of MTA1, and HDAC1 and elevates the Ac-PTEN ratio in tumors. The results suggest that PTER can decrease the expression of MTA1 and destabilize the MTA1/HDAC1 complex allowing acetylation/activation of PTEN on Lys402 site. The expression of MTA1 may be linked to cell apoptosis and invasion in HCC. CONCLUSION: We demonstrated that PTER suppressed the growth, and invasion of HCC and was effective in regulating the levels of the MTA1/HDAC1/NuRD complex, promoting PTEN acetylation and apoptosis in HCC. Our findings suggest that the novel epigenetic nature of PTER anticancer activity opens up new avenues for primary chemoprevention, as well as anticancer and antimetastatic treatment.

Pterostilbene increases PTEN expression through the targeted downregulation of microRNA-19a in hepatocellular carcinoma.

Pterostilbene (Pter) is reported to exhibit an anticancer effect in hepatocellular carcinoma (HCC). In order to explore the anticancer mechanism in HCC cells, the present study aimed to investigate whether pterostilbene (Pter) may increase phosphatase and tensin homolog (PTEN) expression through targeted downregulation of microRNA (miRNA/miR)-19a in hepatocellular carcinoma (HCC). The proliferation, apoptosis and cell cycle was analyzed in the SMMC­7721 HCC cell line by MTT assays and flow cytometry methods. Cells were divided into five treatment groups: Pter treatment, miR­19a inhibitor transfection, Pter + miR­19a inhibitor, negative control transfection and blank control. The expression of miR­19a and PTEN was detected by reverse transcription­quantitative polymerase chain reaction and western blot analysis following treatment. Furthermore, a luciferase reporter gene assay was performed to determine whether the PTEN gene was a direct target of miR­19a. The results demonstrated that Pter treatment or miR­19a inhibitor transfection downregulated miR­19a and induced PTEN/Akt pathway regulation, which led to proliferation inhibition, cell cycle arrest in the S phase, increased apoptosis and reduced cell invasion. These results indicated that Pter may increase PTEN expression through the direct downregulation of miR­19a in HCC. Therefore, miR­19a may have potential as a novel molecular marker for HCC and Pter may be a promising clinical target with the potential to be developed as a HCC therapy.

Tumoricidal activities of pterostilbene depend upon destabilizing the MTA1-NuRD complex and enhancing P53 acetylation in hepatocellular carcinoma.

The present study aimed to assess the tumoricidal effect of metastasis-associated protein 1 (MTA1) induced by pterostilbene (PTER) in hepatocellular carcinoma (HCC). The SMMC-7721 hepatoma cell line was treated with PTER. Following treatment, the mRNA transcript abundance of MTA1 was measured using quantitative polymerase chain reaction. Additionally, cell viability was determined using an MTT assay, and protein expression was measured through western blotting. Cell invasion, motility and apoptosis, as well as the cell cycle, were also investigated. Following PTER treatment, MTA1, histone deacetylase (HDAC) 1 and HDAC2 were downregulated, whereas the ratio of acetyl-p53 to total p53 was increased in HCC cells. Cell viability decreased as the PTER dose increased. MTA1 may be associated with proliferation, motility, invasion and metastasis in HCC cells. PTER appeared to repress cell proliferation, trigger apoptosis, induce cell cycle arrest, and inhibit motility and invasion via MTA1 in human liver cancer cells. The results of the present study demonstrated that PTER can downregulate the MTA1-nucleosome remodeling and deacetylase complex, and enhance p53 acetylation to inhibit the growth of tumor cells in HCC.

The early prevention and treatment of PVST after laparoscopic splenectomy: A prospective cohort study of 130 patients.

BACKGROUND: After laparoscopic splenectomy (LS) in patients with cirrhotic and hypersplenism, there is highly risk of suffering from portal vein system thrombosis (PVST) complication. This study is aimed to investigate the risk factors of PVST and study the anticoagulation effect on the prevention of PVST after LS. MATERIALS AND METHODS: We retrospectively observed 130 patients who performed LS from February 2009 to December 2016. Patients were classified into the anticoagulation group (73 patients) and the non-anticoagulation group (57 patients). At the same time, the non-PVST and PVST groups were used to analyze the factors of thrombosis. RESULTS: We analyzed the risk factors of PVST, the mean platelet volume (MPV), platelet count (PLT), plasma d-dimer, thickness of spleen and portal vein diameter were statistically significant (P < 0.05) between PVST group and non-PVST group. Compared with the non-anticoagulant group, anticoagulant group had a lower incidence of PVST (P = 0.044), a significant lower PLT (P = 0.001), a notable lower mean platelet volume (P = 0.006), and an obvious lower d-dimer (P = 0.001) after LS. And prothrombin time (PT) and international normalized ratio (INR) were significant increase after treated with anticoagulant drugs. Multiple logistic regression analysis reported that PLT, d-dimer, portal vein diameter and thickness of spleen were the risk factors of PVST, however the anticoagulant drug was an independent protective factor for PVST (P = 0.001). CONCLUSIONS: Anticoagulant drug significantly decreased the incidence rate of PVST in patients with cirrhotic and portal hypertension after LS.

Long non-coding RNA PTENP1 interacts with miR-193a-3p to suppress cell migration and invasion through the PTEN pathway in hepatocellular carcinoma.

Long non-coding RNA PTENP1, the pseudogene of PTEN tumor suppressor, was previously reported to be a tumour suppressor in some cancer types. However, the precise effects mediated by PTENP1 transcripts within intricate regulatory networks involving molecular interactions with PTEN and tumorigenicity in hepatocellular carcinoma (HCC) remains elusive. Here, we identify the critical biological functions of PTENP1 and discuss whether PTENP1 could directly interact with miR-193a-3p to affect the progression of HCC both in vitro and in vivo. We demonstrated that PTENP1 level in the HCC tissues was significantly lower compared with those in the adjacent normal tissues. And PTENP1 was able to repress cell invasion, metastasis, and proliferation capacity in HCC cell lines. The overexpression of PTENP1 inhibited HCC growth both in vitro and in vivo. There were a binding sequence and direct interaction between PTENP1 and miR-193a-3p. PTENP1 as an endogenous sponge interacted with miR-193a-3p, leading to regulate the downstream PTEN/Akt pathway. These results suggested that PTENP1 with its suppression effect might serve as novel biomarkers and potent therapeutic strategies in HCC.