• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.2
• /
• pp.885-889
• /
• 2013

microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through post-transcriptional interactions with mRNA. miRNAs have recently emerged as key regulators of various cancers. Although miR-27a has been implicated in several other cancers, its role in hepatitis B virus-related hepatocellular carcinoma (HCC) is unknown. In this study, we showed miR-27a to be frequently up-regulated in HCC tissues and HCC cell lines (HepG2 and Huh7). Overexpression of miR-27a enhanced cell proliferation, promoted migration and invasion, and activated cell cycling in HepG2 and Huh7 cells. In summary, our results suggest that up-regulation of miR-27a may play an oncogenic role in the development of HCC and might thus be a new therapeutic target in HCC patients.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.9
• /
• pp.5391-5396
• /
• 2013

Aim: To investigate the role of Golgi phosphoprotein 3 (GOLPH3) in tumour growth and metastasis of esophageal squamous cancer. Methods: A lentiviral shRNA-vector was utilized to stably knockdown GOLPH3 in Eca-109 esophageal squamous cancer cells. mRNA transcription and protein expression of GOLPH3 were examined by real-time quantitative PCR and Western blotting, respectively. Cell proliferation activity was assessed by MTT assay and invasion and migration potentials by matrigel invasion and transwell motility assays. Results: Stable knockdown in the GOLPH3 cell line was established. PD-A gene expression was significantly suppressed by lentivirus-mediated RNAi, which resulted in reducing the capacity for cell proliferation, migration, invasion and adhesion in vitro. In vivo, GOLPH3 depletion resulted in inhibition of tumour growth, with stable decrease in the expression of GOLPH3 in tumor xenografts. Conclusions: Our findings suggest that lentivirus mediated silencing of the GOLPH3 gene has a significant anti-tumour effect on esophageal squamous cancer in vitro and in vivo. In addition, the results indicate that GOLPH3 might be an effective molecular target for gene therapy in esophageal squamous cancer.

• Plant Resources
• /
• v.8 no.3
• /
• pp.209-216
• /
• 2005

Persicaria thunbergii has been utilized for the treatment of cancer as a folk medicine. We examined the effect of isorhamnetin, a flavonoid isolated from Persicaria thunbergii, on angiogenesis in vitro and in vivo. Basic fibroblast growth factor (bFGF) is a potent angiogenic factor found in various tumors. In this study, we found that the isorhamnetin decreased bFGF-induced human umbilical vein endothelial cells (HUVECs) proliferation and migration in a concentration-dependent manner (5, 10 and $20\;{\mu}M$) whereas, it did not inhibit bFGF-induced capillary-like formation of HUVECs. The chicken chorioallantoic membrane assay revealed that addition of isorhamnetin (10, 20 and $40\;{\mu}M$) displayed an antiangiogenic effect in vivo. These results suggest that the isorhamnetin inhibits the proliferation and migration of endothelial cells induced by bFGF, which may explain its anti-angiogenic properties.

• Biomolecules & Therapeutics
• /
• v.29 no.6
• /
• pp.643-649
• /
• 2021

Literature has revealed that the delta opioid receptor (DOR) exhibited diverse pharmacological effects on neuron and skin. In the present study, we have investigated whether the activation of DOR has hair-growth promotion effects. Compared with other opioid receptor, DOR was highly expressed in epidermal component of hair follicle in human and rodents. The expression of DOR was high in the anagen phase, but it was low in the catagen and telogen phases during mouse hair cycle. Topical application of UFP-512, a specific DOR agonist, significantly accelerated the induction of the anagen in C₃H mice. Topical application of UFP-512 also increased the hair length in hair organ cultures and promoted the proliferation and the migration of outer root sheath (ORS) cells. Similarly, pharmacological inhibition of DOR by naltrindole significantly inhibited the anagen transition process and decreased hair length in hair organ cultures. Thus, we further examined whether Wnt/β-catenin pathway was related to the effects of DOR on hair growth. We found that Wnt/β-catenin pathway was activated by UFP-512 and siRNA for β-catenin attenuated the UFP-512 induced proliferation and migration of ORS cells. Collectively, result established that DOR was involved in hair cycle regulation, and that DOR agonists such as UFP-512 should be developed for novel hair-loss treatment.

• Molecules and Cells
• /
• v.42 no.9
• /
• pp.628-636
• /
• 2019

Altered genetic features in cancer cells lead to a high rate of aerobic glycolysis and metabolic reprogramming that is essential for increased cancer cell viability and rapid proliferation. Pyruvate kinase muscle (PKM) is a rate-limiting enzyme in the final step of glycolysis. Herein, we report that PKM is a potential therapeutic target in triple-negative breast cancer (TNBC) cells. We found that PKM1 or PKM2 is highly expressed in TNBC tissues or cells. Knockdown of PKM significantly suppressed cell proliferation and migration, and strongly reduced S phase and induced G2 phase cell cycle arrest by reducing phosphorylation of the CDC2 protein in TNBC cells. Additionally, knockdown of PKM significantly suppressed $NF-{\kappa}B$ (nuclear factor kappa-light-chain-enhancer of activated B cells) activity by reducing the phosphorylation of p65 at serine 536, and also decreased the expression of $NF-{\kappa}B$ target genes. Taken together, PKM is a potential target that may have therapeutic implications for TNBC cells.

• Journal of Life Science
• /
• v.27 no.1
• /
• pp.1-7
• /
• 2017

Abnormal actin remodeling is a typical characteristic of tumor cells. Thymosin ${\beta}_{10}$ (TB10) and profilin-1 (PFN-1) are actin-binding proteins and essential regulators of actin polymerization. We previously showed that TB10 induced death in ovarian cancer cells by sequestering F-actin, but the underlying mechanisms of this induction have not been explored. In this study, we identified TB10 as a novel regulator of PFN-1 and demonstrated its novel function as a tumor suppressor in ovarian cancer cell lines. The present study investigated protein expression profiles through polyacrylamide gel electrophoresis (PAGE) and liquid chromatography-mass spectroscopy (LC-MS/MS) in SKOV3 cells, an ovarian cancer cell line, that were transiently transfected with TB10. PFN-1 was highly overexpressed in response to TB10, and overexpression of PFN-1 resulted in inhibition of cell proliferation and migration and promotion of cellular apoptosis in ovarian cancer cells. Furthermore, transiently transfected PFN-1 appeared to deactivate the Erk signaling pathway, followed by decreased expression of Elk-1 and Egr-1 in human ovarian cancer cells. Interestingly, PFN-1 did not affect the activation of Akt. The results demonstrated that PFN-1 induced apoptotic cell death and inhibited proliferation and migration in ovarian cancer cells, suggesting that PFN-1 may be valuable in anti-cancer therapy.

• Nutrition Research and Practice
• /
• v.8 no.4
• /
• pp.368-376
• /
• 2014

BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the effects of lycopene on the migration, adhesion, tube formation capacity, and p38 mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor cells (EPCs) cultivated with high glucose (HG) and as well as explore the mechanism behind the protective effects of lycopene on peripheral blood EPCs. MATERIALS/METHODS: Mononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation. EPCs were identified after induction of cellular differentiation. Third generation EPCs were incubated with HG (33 mmol/L) or 10, 30, and $50{\mu}g/mL$ of lycopene plus HG. MTT assay and flow cytometry were performed to assess proliferation and apoptosis of EPCs. EPC migration was assessed by MTT assay with a modified boyden chamber. Adhesion assay was performed by replating EPCs on fibronectin-coated dishes, after which adherent cells were counted. In vitro vasculogenesis activity was assayed by Madrigal network formation assay. Western blotting was performed to analyze protein expression of both phosphorylated and non-phosphorylated p38 MAPK. RESULTS: The proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs treated with 10, 30, and $50{\mu}g/mL$ of lycopene plus HG were all significantly higher comapred to the HG group (P < 0.05). Rates of apoptosis were also significantly lower than that of the HG group. Moreover, lycopene blocked phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal relationship between MAPK inhibition and the protective effects of lycopene against HG-induced cellular injury, we treated cells with SB203580, a phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC injury. CONCLUSIONS: Lycopene promotes proliferation, migration, adhesion, and in vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the underlying molecular mechanism of the protective effects of lycopene against HG-induced EPC injury may involve the p38 MAPK signal transduction pathway. Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting p38 MAPKs.

• Korean Journal of Microbiology
• /
• v.50 no.3
• /
• pp.223-226
• /
• 2014

In the fermented soybean product known as "chungkookjang", diverse bioactive compounds are produced when the soybean proteins are degraded during fermentation. Vascular endothelial cells (EC) are crucial in vein function and the formation of new vessels. A treatment to stimulate formation of new blood vessels is needed in cerebrovascular diseases that lead to ischaemic stroke and heart attack, as well as for diabetic ulcers. VEGF (Vascular Endothelial Growth Factor) simulates EC formation. The effect of Chungkookjang ethanol extract (CEE) on the proliferation of EC was studied. CEE (100, $1000{\mu}g/ml$) and boiled CEE were as effective as VEGF (10 ng/ml) for the proliferation of human umbilical vascular endothelial cells (HUVEC). The effect of CEE on the migration of HUVEC was investigated using sprout analysis. CEE ($100{\mu}g/ml$) was as effective as VEGF (10 ng/ml) for the migration of HUVEC. Isolation of specific peptides influencing the growth and migration of EC is needed.

• Journal of Life Science
• /
• v.26 no.12
• /
• pp.1367-1375
• /
• 2016

Cilostazol is known to be a selective inhibitor of phosphodiesterase III and is generally used to treat stroke. Our previous findings showed that cilostazol enhanced capillary density through angiogenesis after focal cerebral ischemia. Angiogenesis is an important physiological process for promoting revascularization to overcome tissue ischemia. It is a multistep process consisting of endothelial cell proliferation, migration, and tubular structure formation. Here, we examined the modulatory effect of cilostazol at each step of the angiogenic mechanism by using human brain microvascular endothelial cells (HBMECs). We found that cilostazol increased the migration of HBMECs in a dose-dependent manner. However, it did not enhance HBMEC proliferation and capillary-like tube formation. We used a cDNA microarray to analyze the mechanisms of cilostazol in cell migration. We picked five candidate genes that were potentially related to cell migration, and we confirmed the gene expression levels by real-time PCR. The genes phosphoserine aminotransferase 1 (PSAT1) and CCAAT/enhancer binding protein ${\beta}$ ($C/EBP{\beta}$) were up-regulated. The genes tissue factor pathway inhibitor 2 (TFPI2), retinoic acid receptor responder 1 (RARRES1), and RARRES3 were down-regulated. Our observations suggest that cilostazol can promote angiogenesis by promoting endothelial migration. Understanding the cilostazol-modulated regulatory mechanisms in brain endothelial cells may help stimulate blood vessel formation for the treatment of ischemic diseases.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.3
• /
• pp.1037-1047
• /
• 2016

HOX transcription factors are evolutionarily conserved in many different species and are involved in important cellular processes such as morphogenesis, differentiation, and proliferation. They have also recently been implicated in carcinogenesis, but their precise role in cancer, especially in cervical cancer (CC), remains unclear. In this work, using microarray assays followed by the quantitative polymerase chain reaction (qPCR), we found that the expression of 25 HOX genes was downregulated in CC derived cell lines compared with non-tumorigenic keratinocytes. In particular, the expression of HOXA9 was observed as down-modulated in CC-derived cell lines. The expression of HOXA9 has not been previously reported in CC, or in normal keratinocytes of the cervix. We found that normal CC from women without cervical lesions express HOXA9; in contrast, CC cell lines and samples of biopsies from women with CC showed significantly diminished HOXA9 expression. Furthermore, we found that methylation at the first exon of HOXA9 could play an important role in modulating the expression of this gene. Exogenous restoration of HOXA9 expression in CC cell lines decreased cell proliferation and migration, and induced an epithelial-like phenotype. Interestingly, the silencing of human papilloma virus (HPV) E6 and E7 oncogenes induced expression of HOXA9. In conclusion, controlling HOXA9 expression appears to be a necessary step during CC development. Further studies are needed to delineate the role of HOXA9 during malignant progression and to afford more insights into the relationship between downmodulation of HOXA9 and viral HPV oncoprotein expression during cercical cancer development.