• Maxillofacial Plastic and Reconstructive Surgery
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• v.34 no.4
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• pp.239-245
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• 2012

Purpose: Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis and lymphangiogenesis including induction of endothelial cell proliferation, migration and capillary tube formation. E7080 (S1164, Selleck chemical, Houston, TX, USA) is a muti-targeted kinase inhibitor, which targets VEGF receptor-2, 3 (VEGFR-2, 3) and inhibits survival and proliferation of tumor cell. The purpose of this study was to determine the anti-tumor effect of E7080 on oral squamous cell carcinoma. Methods: An oral squamous cell carcinoma cell line, SCC-9 was used in this study. E7080 was applied to SCC-9 cells by 3 different concentrations (1, 5, 10 ${\mu}g/mL$). Control means no application of E7080. The cellular growth was evaluated by real-time cell electronic sensing and MTT assay. The signal transduction was evaluated by Western blotting. Results: In experimental group, SCC-9 cell proliferation was decreased and the VEGFR-3 downstream pathways were inhibited compared with control. Furthermore, increasing the concentration of E7080, the ability of E7080 to disturbance of SCC-9 cell proliferation was increased. Conclusion: Proliferation of SCC-9 cells was inhibited by E7080, which was through by inhibition of VEGFR-3 downstream pathway. In vivo study with E7080 will be required to provide therapeutic benefits in oral squamous cell carcinoma.

• The Journal of Korean Medicine
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• v.27 no.1 s.65
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• pp.23-35
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• 2006

Objectives : This study was conducted to investigate the inhibitory effects of Gaejibokryunghwan on cell proliferation in HeLa cells. Methods : Human uterine cervical carcinoma HeLa cells were cultured in the 1%, 5% and 10% concentration of Gaejibokryunghwan extract solution. All three were cultured for 24 hours, 48 hours and 72 hours each, to examine the inhibitory effects of Gaejibokryunghwan. Afterwards, we drew out the effect of Gaejibokryunghwan extract solution by making 5 analysis. First analysis was to measure the proliferation rate of cells. Second was FACS analysis. Third was to estimate the activity or caspase-3. Fourth, we used XTT assay to analyze the activation or cells. Ana lastly, a molecular biological method was used to determine activation of MAP kinase in the HeLa cells. Results : After 24, 48 and 72 hours cultivation, the proliferation of HeLa cells showed the dose-dependent decrease in all Gaejibokryunghwan extract solution groups compared to the control group. In the FACS analysis, Gaejibokryunghwan extract solution groups showed increased caspase expression compared to the control group, except for the group for 48 and 72 hours in 1 % concentrate. Caspase-3 activities were increased in all, except tile group cultured for 24 hours in 5% concentrate and the groups cultured for 48 hours in 1% and 5% concentrate. In the XTT study, 1% Gaejibokryunghwan extract solution groups showed increase compared to the control group, but other Gaejibokryunghwan extract solution containing groups showed significant decrease compared to the control after 24, 48 and 72 hours of cultivation. The expressions of MAP kinase were decreased in all Gaejibokryunghwan extract solution containing groups compared to the control group after 24, 48 and 72 hours of cultivation. Conclusions : From this study, we could suggest that Gaejibokryunghwan be available to the inhibition of proliferation of human cervical carcinoma cell line, HeLa cells in vitro.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6419-6425
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• 2013

Background: Neoadjuvant chemotherapy (NACT) is a treatment modality whereby chemotherapy is used as the initial treatment of HNSCC in patients presenting with advanced cancer that cannot be treated by other means. It leads to shrinkage of tumours to an operable size without significant compromise to essential oro-facial organs of the patients. The molecular mechanisms behind shrinkage due to NACT is not well elucidated. Materials and Methods: Eleven pairs of primary HNSCCs and adjacent normal epithelium, before and after chemotherapy were screened for cell proliferation and apoptosis. This was followed by immunohistochemical analysis of some cell cycle (LIMD1, RBSP3, CDC25A, CCND1, cMYC, RB, pRB), DNA repair (MLH1, p53) and apoptosis (BAX, BCL2) associated proteins in the same set of samples. Results: Significant decrease in proliferation index and increase in apoptotic index was observed in post-therapy tumors compared to pre-therapy. Increase in the RB/pRB ratio, along with higher expression of RBSP3 and LIMD1 and lower expression of cMYC were observed in post-therapy tumours, while CCND1 and CDC25A remained unchanged. While MLH1 remained unchanged, p53 showed higher expression in post-therapy tumors, indicating inhibition of cell proliferation and induction of apoptosis. Increase in the BAX/BCL2 ratio was observed in post-therapy tumours, indicating up-regulation of apoptosis in response to therapy. Conclusions: Thus, modulation of the G1/S cell cycle regulatory proteins and apoptosis associated proteins might play an important role in tumour shrinkage due to NACT.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1017-1021
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• 2013

The cellular apoptosis susceptibility (CSE1L) gene has been demonstrated to regulate multiple cellular mechanisms including the mitotic spindle check point as well as proliferation and apoptosis. However, the importance of CSE1L in human colon cancer is largely unknown. In the present study, we examined expression levels of CSE1L mRNA by semiquantitative RT-PCR. A lentivirus-mediated small interfering RNA (siRNA) was used to knock down CSE1L expression in the human colon cancer cell line RKO. Changes in CSE1L target gene expression were determined by RT-PCR. Cell proliferation was examined by a high content screening assay. In vitro tumorigenesis was measured by colony-formation assay. Cell cycle distribution and apoptosis were detected by flow cytometric analysis. We found CSE1L mRNA to be expressed in human colon cancer cells. Using a lentivirus based RNAi approach, CSE1L expression was significantly inhibited in RKO cells, causing cell cycle arrest in the G2/M and S phases and a delay in cell proliferation, as well as induction of apoptosis and an inhibition of colony growth capacity. Collectively, the results suggest that silencing of CSE1L may be a potential therapeutic approach for colon cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1262-1269
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• 2008

Low intensity pulsed ultrasound(LIPUS) is known to accelerate bone regeneration, but the precise cellular signaling mechanism is still unclear. The purpose if this study was to determine the effect of LIPUS on the signaling mechanism of rat chondrocyte. In the explant culture condition, there was inhibition effect of 1 $W/cm^2$ intensity LIPUS on chondrocytes proliferation but chondrocytes proliferation was increased at 0.25 $W/cm^2$ intensity. In addition, western blot analysis of MAPKs showed that LIPUS increased ERK1/2 activity from the 10 min treatment of LIPUS. Hydrogen peroxide($H_2O_2$), resulted in a time- and dose-dependent cell proliferation, which was largely attributed to apoptosis. $H_2O_2$ treatment caused marked sustained nucleus condensation in Hoechst stain. LIPUS and $H_2O_2$ activates phosphorylation of p-ERK1/2 and PD 98059($10^{-5}M$) blocked the effect of LIPUS and $H_2O_2$. Moreover, the synergistic phosphorylation of p44/42 MAPK by $H_2O_2$, LIPUS was selectively inhibited by PD 98059, ERK1/2 inhibitor. In order to determine whether the increase in cell proliferation caused by $H_2O_2$ and LIPUS could be explained by changes in the level of the prostaglandin $E_2$. Our study demonstrated that LIPUS stimulate the cell proliferation via activated phosphorylation of ERK1/2 in condrocyte. LIPUS has anabolic effects on rat cartilage in explant cultures, indicating a potential important method for the treatment of osteoarthritic cartilarge.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.8
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• pp.983-988
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• 2007

Epigallocatechin gallate (EGCG), a principal antioxidant derived from green tea, is one of the most extensively investigated chemopreventive phytochemicals. However, the effect of EGCG on proliferation in MDA-MB-231 breast cancer cell is not well known. We investigated the effect of EGCG on protein and mRNA expression related to cell proliferation in MDA-MB-231 human breast cancer cell lines. We cultured MDA-MB-231 cells in the presence of 0, 5, 10 and 20 ${\mu}m$ of EGCG. EGCG significantly inhibited the cancer cell proliferation (p<0.05). In MDA-MB-231 huamn breast cancer cell, EGCG lowered $ErbB_2$ and $ErbB_3$ protein as well as mRNA expression. In addition, protein and mRNA expression of phosphorylated Akt and total Akt were significantly decreased (p<0.05). We suggest that EGCG inhibits cell proliferation through $ErbB_2$, $ErbB_3$ and Akt cell signaling.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.107-113
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• 2009

Olibanum (Boswellia serrata) has been shown to have anti-inflammatory, anti-arthritic and anticancer effects. This study determined the role of a water extract of olibanum in platelet-derived growth factor (PDGF)-stimulated proliferation and migration of rat aortic smooth muscle cells (RASMCs). PDGF-BB induced the migration and proliferation of RASMCs that were inhibited by olibanum extract in a dose-dependent manner. The PDGF-BB-increased phosphorylation of p38 mitogen-activated protein kinase (MAPK); the heat shock protein (Hsp) 27 was significantly inhibited by the olibanum extract. The effects of PDGF-BB-induced extracellular signal-regulated kinase1/2 was not altered by the olibanum extract. Treatment with olibanum extract inhibited PDGF-BB-stimulated sprout out growth of aortic rings. These results suggest that the water extract of olibanum inhibits PDGF-BB-stimulated migration and proliferation in RASMCs as well as sprout out growth, which may be mediated by the inhibition of the p38 MAPK and Hsp27 pathways.

• Journal of Nutrition and Health
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• v.38 no.8
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• pp.656-662
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• 2005

Ginger (Zingiber of oficinale Roscoe, Zingiberaceae) is one of the most frequently and heavily consumed dietary condiments throughout the world. Besides its extensive use as a spice, the rhizome of ginger has also been used in traditional oriental herbal medicine for the management of symptoms such as common cold, digestive disorders, rheumatism, neurologia, colic, and motion-sickness. The oleoresin from rhizomes of ginger contains [6] -gingerol (1- [4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone) and its homologs as pungent ingredients that have been found to possess many interesting pharmacological and physiological activities, such as anti-inflammatory, analgesic, antipyretic, antiheatotoxic, and cardiotonic effects. However, the effect of [6]-gingerol on cell proliferation in breast cancer cell are not currently well known. Therefore, in this study, we examined effect of [6]-gingerol on protein and mRNA expression associated with cell proliferation in MDA-MB-231 human breast. cancer cell lines. We cultured MDA-MB-231 cells in presence of 0, 2.5, 5 and $10{\mu}M$ of [6] -gingerol. [6]-Gingerol inhibited breast cancer cell growth in a dose-depenent manner as determined by MTT assay. ErbB2 and ErbB3 protein and mRNA expression were decreased dose-dependently in cells treated with [6]-gingerol (p<0.05). In addition, phosphorylated Akt levels and total hぉ levels were markedly decreased in cells treated with $2.5{\mu}M$ [6]-gingerol (p<0.05). In conclusion, we have shown that [6]-gingerol inhibits cell proliferation through ErbB2 and ErbB3, reduction in MDA-MB-231 human breast cancer cell lines.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.8.1-8.12
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• 2018

FAM46B is a member of the family with sequence similarity 46. Little is known about the expression and functional role (s) of FAM46B in prostate cancer (PC). In this study, the expression of FAM46B expression in The Cancer Genome Atlas, GSE55945, and an independent hospital database was measured by bioinformatics and real-time PCR analysis. After PC cells were transfected with siRNA or a recombinant vector in the absence or presence of a ${\beta}$-catenin signaling inhibitor (XAV-939), the expression levels of FAM46B, C-myc, Cyclin D1, and ${\beta}$-catenin were measured by western blot and realtime PCR. Cell cycle progression and cell proliferation were measured by flow cytometry and the CCK-8 assay. The effects of FAM46B on tumor growth and protein expression in nude mice with PC tumor xenografts were also measured. Our results showed that FAM46B was downregulated but that ${\beta}$-catenin was upregulated in patients with PC. FAM46B silencing promoted cell proliferation and cell cycle progression in PC, which were abrogated by XAV-939. Moreover, FAM46B overexpression inhibited PC cell cycle progression and cell proliferation in vitro and tumor growth in vivo. FAM46B silencing promoted ${\beta}$-catenin protein expression through the inhibition of ${\beta}$-catenin ubiquitination. Our data clearly show that FAM46B inhibits cell proliferation and cell cycle progression in PC through ubiquitination of ${\beta}$-catenin.

• Tissue Engineering and Regenerative Medicine
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• v.15 no.6
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• pp.781-791
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• 2018

BACKGROUND: Glucosamine hydrochloride (GlcN HCl) has been shown to inhibit cell growth and matrix synthesis, but not with N-acetyl-glucosamine (GlcNAc) supplementation. This effect might be related to an inhibition of critical growth factors (GF), or to a different metabolization of the two glucosamine derivatives. The aim of the present study was to evaluate the synergy between GlcN HCl, GlcNAc, and GF on proliferation and cartilage matrix synthesis. METHOD: Bovine chondrocytes were cultivated in monolayers for 48 h and in three-dimensional (3D) chitosan scaffolds for 30 days in perfusion bioreactors. Serum-free (SF) medium was supplemented with either growth factors (GF) $TGF-{\beta}$ ($5ng\;mL^{-1}$) and IGF-I ($10ng\;mL^{-1}$), GlcN HCl or GlcNAc at 1mM each or both. Six groups were compared according to medium supplementation: (a) SF control; (b) SF + GlcN HCl; (c) SF + GlcNAc; (d) SF + GF; (e) SF + GF + GlcN HCl; and (f) SF + GF + GlcNAc. Cell proliferation, proteoglycan, collagen I (COL1), and collagen II (COL2) synthesis were evaluated. RESULTS: The two glucosamines showed opposite effects in monolayer culture: GlcN HCl significantly reduced proliferation and GlcNAc significantly augmented cellular metabolism. In the 30 days 3D culture, the GlcN HCl added to GF stimulated cell proliferation more than when compared to GF only, but the proteoglycan synthesis was smaller than GF. However, GlcNAc added to GF improved the cell proliferation and proteoglycan synthesis more than when compared to GF and GF/GlcN HCl. The synthesis of COL1 and COL2 was observed in all groups containing GF. CONCLUSION: GlcN HCl and GlcNAc increased cell growth and stimulated COL2 synthesis in long-time 3D culture. However, only GlcNAc added to GF improved proteoglycan synthesis.