Search

Background: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide owing to its high rates of metastasis and recurrence. The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitously overexpressed in several human cancers, including liver, ovary, lung, large intestine, gastric, bone marrow, and breast malignancies and is involved in the invasion and metastasis of cancer cells. Therefore, we aimed to determine the biological role and molecular mechanism of IQGAP3 in HCC.Methods: We used 120 archived clinical HCC samples, 9 snap-frozen HCC tumor tissues, and 4 normal liver tissues. Expression of IQGAP3 mRNA and protein in HCC cell lines (Hep3B, SMMC-7721, HCCC-9810, HepG2, BEL-7404, HCCLM3, QGY-7701, Huh7, and MHCC97H) and normal liver epithelial cells LO2 was examined by western blot, quantitative polymerase chain reaction, and immunohistochemistry. In addition, wound-healing and transwell matrix penetration assays were used to assess the migratory and invasive abilities of HCC cells, respectively.Results: Expression of the IQGAP3 was robustly upregulated in HCC cells and tissues. High expression of IQGAP3 in HCC correlated with aggressive clinicopathological features and was an independent poor prognostic factor for overall survival. Furthermore, ectopic expression of IQGAP3 markedly enhanced HCC cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) in vitro and promoted metastasis of orthotopic hepatic tumors in nude mice. Conversely, silencing endogenous IQGAP3 showed an opposite effect. Mechanistically, IQGAP3 promoted EMT and metastasis by activating TGF-β signaling.Conclusions: IQGAP3 functions as an important regulator of metastasis and EMT by constitutively activating the TGF-β signaling pathway in HCC. Our findings present new evidence of the role of IQGAP3 in EMT and metastasis, indicating its potential as a prognostic biomarker candidate and a therapeutic target against HCC. [ABSTRACT FROM AUTHOR]

A phytochemical investigation of Smilax riparia A. DC. resulted in the isolation of a new aurone ( 1) and 13 known compounds ( 2-14). The structure of the new aurone was determined to be 4,5,3′,4′,5′-pentamethoxy-6-hydroxyaurone on the basis of spectroscopic methods. Compounds 3-11 were isolated from this genus for the first time. Compounds 3 and 4 significantly inhibited the migration of MDA-MB-231 breast cancer cells induced by the chemokine epithelial growth factor (EGF). In addition, compounds 3, 4, and 8 showed significant effects on enhancing GLUT4 translocation in skeletal muscle cells L6myc. [ABSTRACT FROM AUTHOR]

Our research group showed that E-salignone inhibited the invasion of human breast cancer MDA-MB-231 cells induced by the chemokine epidermal growth factor (EGF). Due to the limited natural resources, we had to prepare sizable quantities of E-salignone for the antimetastasis investigation. E-Salignone was synthesized by methylation of the corresponding amine by reductive amination with paraformaldehyde in the presence of sodium triacetoxyhydroborate. The synthesized E-salignone exhibited significant inhibitory effects on the invasion of human MDA-MB-231 breast cancer cells and non-small cell lung cancer cells (A549) induced by the chemokine EGF with IC values of 0.36 μM and 5.77 μM, respectively. Since angiogenesis is required for tumor metastasis, anti-angiogenesis is consider a promising approach for tumor therapy. In our investigation of antimetastatic activity, E-salignone potently inhibited the migration of HUVEC and MDA-MB-231 in the wound healing assay. [ABSTRACT FROM AUTHOR]

Three new pregnane alkaloids, named terminamines H–J (1–3), together with two known alkaloids (4 and 5), were isolated from the ethanol extract of Pachysandra terminalis. The structures of isolated compounds were elucidated by spectroscopic methods, including 1H and 13C NMR, 2D NMR, and HR-ESI-MS. Compounds 1, 4, and 5 revealed significant anti-metastasis activities. In addition, compound 1 inhibited the expression of p-PKCζ in MDA-MB-231 cells, and compound 4 inhibited the expressions of p-PKCζ in MDA-MB-231 and A549 cells. [ABSTRACT FROM AUTHOR]

Background LncRNA promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) is reportedly dysregulated in various cancers. We performed this meta-analysis to clarify the efficacy of PANDAR as a prognostic marker in malignant tumors. Methods The PubMed, Medline, OVID, Cochrane Library, and Web of Science databases were searched from inception to July 3, 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between PANDAR expression and overall survival (OS). Odds ratios (ORs) were calculated to assess the association between PANDAR expression and pathological parameters. Results Eight original studies covering 1,132 cancer patients were included. The pooled HR suggested that high PANDAR expression correlated with poor OS (pooled HR = 1.60, 95% CI: 1.09–2.33) in cancer patients. PANDAR expression was also related to lymph node metastasis (OR = 3.26, 95% CI: 2.09–5.09), advanced tumor stage (OR = 3.60, 95% CI: 2.39–5.44) and histological grade (OR = 2.75, 95% CI: 1.73–4.38). Begg's funnel plot showed no evidence of obvious asymmetry for overall survival and lymph node metastasis. Conclusions Thus high PANDAR expression appears predictive of poor OS, lymph node metastasis, advanced tumor stage and histological grade in multiple cancers. This suggests PANDAR expression could serve as a biomarker of poor prognosis in Chinese cancer patients. [ABSTRACT FROM AUTHOR]

Novel chiral ionone alkaloid derivatives were synthesized and evaluated their anti-metastatic effects in human MDA-MB-231 breast cancer cells. The chiral center C-6 of derivatives exerted an important role in response to the anti-metastatic activity. Comparing with a positive control of LY294002, compounds 17b and 19a exhibited potent inhibitory effects on the EGF-induced invasion of MDA-MB-231 cells with IC 50 values of 0.026 ± 0.003 and 0.016 ± 0.002 μM, respectively. Moreover, compounds 17b and 19a showed inhibitory effects on the expressions of p-PKCζ and p-integrin β1 in MDA-MB-231 cells in a dose-dependent manner. Thus, compounds 17b and 19a offer potential to be developed as novel anti-metastasis agents. [ABSTRACT FROM AUTHOR]

[Display omitted] • Chiral ionone alkaloid ION-31a inhibits breast cancer metastasis and angiogenesis. • Its direct target was identified as HSP90α. • ION-31a downregulates HSP90/HIF-1α/VEGF/VEGFR2 pathway. Breast cancer has become the number one killer of women. In our previous study, an active compound, ION-31a, with potential anti-metastasis activity against breast cancer was identified through the synthesis of ionone alkaloid derivatives. In the present study, we aimed to identify the therapeutic target of ION-31a. We used a fluorescence tag labeled probe, molecular docking simulation, and surface plasmon resonance (SPR) analysis to identify the target of ION-31a. The main target of ION-31a was identified as heat shock protein 90 (HSP90). Thus, ION-31a is a novel HSP90 inhibiter that could suppress the metastasis of breast cancer and angiogenesis significantly in vitro and in vivo. ION-31a acts via inhibiting the HSP90/hypoxia inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway and downregulating downstream signal pathways, including protein kinase B (AKT)/mammalian target of rapamycin (mTOR), AKT2/protein kinase C epsilon (PKCζ), extracellular regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and mitogen-activated protein kinase 14 (p38MAPK) pathways. ION-31a affects multiple effectors implicated in tumor metastasis and has the potential to be developed as an anti-metastatic agent to treat patients with breast cancer. [ABSTRACT FROM AUTHOR]