• Asian Pacific Journal of Cancer Prevention
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• v.17 no.2
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• pp.615-618
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• 2016

Ethyl acetate extracts obtained from culture of endophytic fungi Aspergillus sp isolated from Piper crocatum Ruiz & Pav, have been shown to possess cytotoxic activity against T47D breast cancer cells. Investigations were here conducted to determine bioactive compounds responsible for the activity. Bioassay guided fractionation was employed to obtain active compounds. Structure elucidation was performed based on analysis of LC-MS, $^1H$-NMR, $^{13}C$-NMR, COSY, DEPT, HMQC, HMBC data. Cytotoxity assays were conducted in 96 well plates against T47D and Vero cell lines. Bioassay guided isolation and chemical investigation led to the isolation of pyrophen, a 4-methoxy-6-(1'-acetamido-2'-phenylethyl)-2H-pyran-2-one. Further analysis of its activity against T47D and Vero cells showed an ability to inhibit the growth of T47D cells with IC50 values of $9.2{\mu}g/mL$ but less cytotoxicity to Vero cells with an $IC_{50}$ of $109{\mu}g/mL$. This compound at a concentration of 400 ng/mL induced S-phase arrest in T47D cells.

• Journal of dental hygiene science
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• v.3 no.1
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• pp.11-14
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• 2003

A methylotrophic Actinomycetes strain, which produce the anti-oral cancer activity compound, was isolated from soil and estimated as Amylocolatosis sp. based on taxonomic studies. A methanol didn't have influence on the production of the anticancer compounds. These compound were isolated by ethylacetate extract, silica gel column chromatography, sephadex LH-20 column and reverse phase HPLC. The compounds were very stable under heat ($121^{\circ}C$), acid(pH 2.0) and alkali(pH 11.0) treatment. The cytotoxic effect of isolated anticancer compounds on various cancer cell lines such as A549, SNU-1, KB, L1210, and Sarcoma 180 was investigated by MTT assay method. And these produced compounds also showed the broad antimicrobial spectrum to test strains such as bacteria and yeast.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2973-2978
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• 2013

Maesil (Prunus mume Siebold & Zucc.), a member of the genus Rosaceae, has been reported to have antioxidative effects, as well as anticancer influence in many cancer lines. Thus, this present study was designed to investigate the inhibitory effect of fermented Maesil with probiotics against 7,12-dimethylbenz[a]anthracene (DMBA), 12-O-tetradecanoyl phorbol 13-acetate (TPA)-induced mouse skin carcinogenesis via its antioxidative potential. Mice were fed a diet containing fermented Maesil, containing either 1% (1% FM fed group) or 2% (2% FM fed group) along with probiotics following DMBA and TPA exposure. Continuous ingestion of the experimental feed markedly inhibited skin carcinogenesis, as evidenced by a marked decrease in papilloma numbers and epidermal hyperplasia as well as cellular proliferation and the percentage of proliferating-cell nuclear antigen positive cells. Also, the FM fed group showed an increase of total antioxidant capacity as well as an increased level of phase II detoxifying enzymes such as superoxide dismutase, concurrent with a decreased lipid peroxidation activity level. Taken together, these results suggest that fermented Maesil has the ability to suppress the development of DMBA-TPA induced skin carcinogenesis, via the reduction of lipid peroxidation, enhancing total antioxidant capacity and phase II detoxifying enzyme.

• Molecules and Cells
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• v.37 no.11
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• pp.812-818
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• 2014

This study was to investigate the mechanism and role of Kif4A in doxorubicin-induced apoptosis in breast cancer. Using two human breast cancer cell lines MCF-7 (with wild-type p53) and MDA-MB-231 (with mutant p53), we quantitated the expression levels of kinesin super-family protein 4A (Kif4A) and poly (ADP-ribose) Polymerase-1 (PARP-1) by Western blot after doxorubicin treatment and examined the apoptosis by flow cytometry after treatment with doxorubicin and PARP-1 inhibitor, 3-Aminobenzamide (3-ABA). Our results showed that doxorubicin treatment could induce the apoptosis of MCF-7 and MDA-MB-231 cells, the down-regulation of Kif4A and upregulation of poly(ADP-ribose) (PAR). The activity of PARP-1 or PARP-1 activation was significantly elevated by doxorubicin treatment in dose- and time-dependent manners (P < 0.05), while doxorubicin treatment only slightly elevated the level of cleaved fragments of PARP-1 (P > 0.05). We further demonstrated that overexpression of Kif4A could reduce the level of PAR and significantly increase apoptosis. The effect of doxorubicin on apoptosis was more profound in MCF-7 cells compared with MDA-MB-231 cells (P < 0.05). Taken together, our results suggest that the novel role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells is achieved by inhibiting the activity of PARP-1.

• Journal of Gastric Cancer
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• v.22 no.4
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• pp.319-338
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• 2022

Purpose: Gastric cancer (GC) has high morbidity and mortality, the cure rate of surgical treatment and drug chemotherapy is not ideal. Therefore, development of new treatment strategies is necessary. We aimed to identify the mechanism underlying Sp1 regulation of GC progression. Methods and Methods: The levels of Sp1, β-catenin, SET domain bifurcated 1 (SETDB1), and 15-hydroxyprostaglandin dehydrogenase (HPGD) were detected by quantitative reverse transcription polymerase chain reaction and western blot analysis. The targets of SETDB1 were predicted by AnimalTFDB, and dual-luciferase reporter assay was used for confirming the combination of Sp1, β-catenin, and SETDB1. HGC27 or AGS cells (1×10⁶ cells/mouse) were injected into mice via the caudal vein for GC model establishment. The level of Ki67 was detected using immunohistochemistry, and hematoxylin and eosin staining was performed for evaluating tumor metastasis in mice with GC. Results: HPGD was inhibited, while the protein levels of Sp1, β-catenin, and SETDB1 were up-regulated in GC tissues and cell lines. HPGD overexpression or SETDB1 silencing inhibited the proliferation, invasion, and migration of GC cells, and Sp1 regulated the proliferation, invasion, and migration of GC cells in a β-catenin-dependent manner. Furthermore, HPGD served as a target of SETDB1, and it was negatively regulated by SETDB1; additionally, Sp1 and β-catenin bound to the SETDB1 promoter and negatively regulated HPGD expression. We proved that Sp1 regulated GC progression via the SETDB1/HPGD axis. Conclusions: Our findings revealed that Sp1 transcriptionally inhibited HPGD via SETDB1 in a β-catenin-dependent manner and promoted the proliferation and metastasis of GC cells.

• Journal of the Korean Society of Food Culture
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• v.24 no.6
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• pp.749-755
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• 2009

We investigated the chemical components of red onion powder dried using the low temperature vacuum method and the inhibitory effects of solvent extracts of the dried red onion powder on the growth of HT-1080 human fibrosarcoma and HT-29 human colon cancer cells and $H_2O_2$-induced oxidative stress. The moisture content of the dried red onion powder was 17.95%, while the vitamin C content was 96 mg/100 g and the total phenols content was 39.1 mg/mL. The inhibitory effects of acetone with methylene chloride (A+M) and methanol (MeOH) extracts of the red onion powder on the growth of HT-1080 and HT-29 cancer cells increased in a dose dependent manner (p<0.05). The inhibitory effect was greater on the growth of HT-29 cells, while the A+M extracts had a higher inhibitory effect than the MeOH extracts. Treatment with the hexane, 85% aq. methanol, butanol and water fractions of the extract led to significant inhibition of the growth of both cancer cell lines (p<0.05). Among the fractions, the hexane and 85% aq. methanol fractions showed a greater inhibitory effect. To determine the protective effect on $H_2O_2$-induced oxidative stress, a DCFH-DA (dichlorodihydrofluorescin diacetate) assay was conducted. All fractions, including the crude extracts of dried red onion, appeared to lead to a significant reduction in the levels of intracellular reactive oxygen species (ROS), and these reductions occurred in a dose dependent fashion (p<0.05). Among the fractions, the 85% methanol fraction showed the greatest protective effect on the production of lipid peroxides.

• BMB Reports
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• v.51 no.12
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• pp.630-635
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• 2018

C-X-C motif chemokine ligand 2 (CXCL2) is a small secreted protein that exhibits a structure similar to the proangiogenic subgroup of the CXC chemokine family. Recently, accumulating evidence suggests that chemokines play a pivotal role in cancer progression and carcinogenesis. We examined the expression levels of 7 types of $ELR^+$ CXCLs messenger RNA (mRNA) in 264 clinical samples. We found that CXCL2 expression was stably down-regulated in 94% of hepatocellular carcinoma (HCC) specimens compared with paired adjacent normal liver tissues and some HCC cell lines. Moreover, CXCL2 overexpression profoundly attenuated HCC cell proliferation and growth and induced apoptosis in vitro. In animal studies, we found that overexpressing CXCL2 by lentivirus also apparently inhibited the size and weight of subcutaneous tumours in nude mice. Furthermore, we demonstrated that CXCL2 induced HCC cell apoptosis via both nuclear and mitochondrial apoptosis pathways. Our results indicate that CXCL2 negatively regulates the cell cycle in HCC cells via the ERK1/2 signalling pathway. These results provide new insights into HCC and may ultimately lead to the discovery of innovative therapeutic approaches of HCC.

• The Journal of Internal Korean Medicine
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• v.30 no.4
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• pp.845-857
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• 2009

Background and Objectives : Korean mistletoe lectin (Viscum album coloratum agglutinin, VCA) and bee venom (BV) have been reported to induce apoptosis in various cancer cell lines in vitro and to show antitumor activity against a variety of tumors in animal models. However, the comparative effect of VCA and BV on the anti-cancer effect and mechanisms of action has not been determined. In this study, the effect in a human hepatocellular carcinoma cell line, Hep G2 cells, was examined. Methods : Cytotoxic effects of VCA and BV on Hep G2 cells were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay in litro. The apoptotic cell death was then confirmed by propidium iodide staining and DNA fragmentation analysis. The mechanisms of action were examined by the expression of anti-apoptotic proteins and activation of mitogen-activated protein kinases. The involvement of kinase was examined in VCA or BV-induced apoptosis by using kinase inhibitors. Results : VCA and BV killed Hep G2 cells in a time and dose-dependent manner. Treatment of Hep G2 cells with VCA activated poly (ADP-ribose) polymerase-1 (PARP-1) known as a marker of apoptosis, and mitogen-activated protein kinases signaling pathways including MAPK/ERK, p38 MAPK and JNK. BV also activated PARP-1, MAPK/ERK. and p38 MAPK but not JNK. The expression level of anti-apoptotic molecule, Bcl-X, was decreased by VCA treatment but not by BV. Finally, the phosphorylation level of ERM proteins involved in the cytoskeleton homeostasis was decreased by both stimuli. VCA-induced apoptosis was partially inhibited by in the presence of JNK and p38 inhibitor, but BV only by p38 inhibitor. Conclusions : VCA-induced apoptosis is dependent on the activation of p38 and JNK. while BV-induced apoptosis is mediated by p38 activation in Hep G2 cells.

• Molecules and Cells
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• v.41 no.5
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• pp.423-435
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• 2018

This investigation was aimed at working out the combined role of lncRNA H19, miR-29b and Wnt signaling in the development of colorectal cancer (CRC). In the aggregate, 185 CRC tissues and corresponding para-carcinoma tissues were gathered. The human CRC cell lines (i.e. HT29, HCT116, SW480 and SW620) and normal colorectal mucosa cell line (NCM460) were also purchased. Si-H19, si-NC, miR-29b-3p mimics, miR-29b-3p inhibitor, si-PGRN and negative control (NC) were, respectively, transfected into the CRC cells. Luciferase reporter plasmids were prepared to evaluate the transduction activity of $Wnt/{\beta}-catenin$ signaling pathway, and dual-luciferase reporter gene assay was arranged to confirm the targeted relationship between H19 and miR-29b-3p, as well as between miR-29b-3p and PGRN. Finally, the proliferative and invasive capacities of CRC cells were appraised through transwell, MTT and scratch assays. As a result, overexpressed H19 and down-expressed miR-29b-3p displayed close associations with the CRC patients' poor prognosis (P < 0.05). Besides, transfection with si-H19, miR-29b-3p mimic or si-PGRN were correlated with elevated E-cadherin expression, decreased snail and vimentin expressions, as well as less-motivated cell proliferation and cell metastasis (P < 0.05). Moreover, H19 was verified to directly target miR-29b-3p based on the luciferase reporter gene assay (P < 0.05), and miR-29b-3p also bound to PGRN in a direct manner (P < 0.05). Finally, addition of LiCl ($Wnt/{\beta}-catenin$ pathway activator) or XAV93920 ($Wnt/{\beta}-catenin$ pathway inhibitor) would cause remarkably altered E-cadherin, c-Myc, vimentin and snail expressions, as well as significantly changed transcriptional activity of ${\beta}-catenin/Tcf$ reporter plasmid (P < 0.05). In conclusion, the lncRNA H19/miR-29b-3p/PGRN/Wnt axis counted a great deal for seeking appropriate diagnostic biomarkers and treatment targets for CRC.

• Archives of Pharmacal Research
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• v.23 no.1
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• pp.35-41
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• 2000

In order to investigate the stereochemical requirements of planar structure at 4-position of 4-phenyl-1-arylsulfonylimidazolidinones (1) for their cytoxicities against human cancer cell lines, the size, the distance from imidazolidinone ring, and the conformation of this moiety were variegated. Replacement of phenyl moiety with naphthyl in compounds 2 and 3 or benzyl moiety in compound 4 sharply reduced activity of 1. Conformational restriction on phenyl ring in compound 5 also resulted in the loss of activity of 1. Therefore, phenyl moiety without any substituents directly attached to imidazolidinone ring of 1 should be considered as an essential pharmacophore for this analog.