• Journal of Nutrition and Health
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• v.30 no.8
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• pp.987-994
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• 1997

To investigate the effects of n-3 fatty acids on breast cancer, MDA-MB231 human breast cancer cells were cultured in the presence of $\alpha$-linolenic (LNA), eicosapentaenoic(EPA), and docosahexaenoic acid (DHA) at a concentration of 0.5$\mu\textrm{g}$/ml in serum -free IMM medium. Cell growth was monitored and thiobarbituric acid reactive substances (TBARS), $\alpha$-tocopherol contents, and oncogene expression were measured. To compare the effects of n-3 fatty acids with other types of fatty acid, steraic (STA), olieic(OA). linoleic acid(LA) were used. After one day , cell growth was retarded most highly when DHA was in the medium. Cellular TBARS level measured after three days of culture was the highest with DHA in the medium and was also increased by LNA and EPA, compared with STA, OA and LA. Alpha-tocoopherol contents of cells were decreased by DHA but only modestly. There was non significant difference in $\alpha$-tocopherol contents in cells cultured in the presence of the other fatty acids. northern blot hybridization carried out with cells cultured during 24 hours showed that levels of erbB-2 mRNA were not altered by six different fatty acids in the medium but those of c-myc were transiently decreased in the early period by both n-6 and n-3 polyunsaturated fatty acids. The level of tumor suppressor gen p53 mRNA , however, was increased by DHA with time. It is concluded that the cytotoxicity of lipid peroxide and increased expression of tumor suppressor gene p53 are at least partly responsible for the inhibitory effect of DHA on growth of breast cancer cells.

• Molecules and Cells
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• v.45 no.6
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• pp.425-434
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• 2022

The post-translational modification (e.g., phosphorylation) of estrogen receptor α (ERα) plays a role in controlling the expression and subcellular localization of ERα as well as its sensitivity to hormone response. Here, we show that ERα is also modified by UFM1 and this modification (ufmylation) plays a crucial role in promoting the stability and transactivity of ERα, which in turn promotes breast cancer development. The elevation of ufmylation via the knockdown of UFSP2 (the UFM1-deconjugating enzyme in humans) dramatically increases ERα stability by inhibiting ubiquitination. In contrast, ERα stability is decreased by the prevention of ufmylation via the silencing of UBA5 (the UFM1-activating E1 enzyme). Lys171 and Lys180 of ERα were identified as the major UFM1 acceptor sites, and the replacement of both Lys residues by Arg (2KR mutation) markedly reduced ERα stability. Moreover, the 2KR mutation abrogated the 17β-estradiol-induced transactivity of ERα and the expression of its downstream target genes, including pS2, cyclin D1, and c-Myc; this indicates that ERα ufmylation is required for its transactivation function. In addition, the 2KR mutation prevented anchorage-independent colony formation by MCF7 cells. Most notably, the expression of UFM1 and its conjugating machinery (i.e., UBA5, UFC1, UFL1, and UFBP1) were dramatically upregulated in ERα-positive breast cancer cell lines and tissues. Collectively, these findings implicate a critical role attributed to ERα ufmylation in breast cancer development by ameliorating its stability and transactivity.

• Journal of Life Science
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• v.31 no.10
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• pp.873-884
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• 2021

The purpose of present study is to investigate the role of artesunate (ART) in enhancing anticancer effect of nonsteroidal anti-inflammatory drug (NSAID) on human cancer cells, and we elucidate a possible molecular mechanism of this combination effect. We showed that the combined effect of ART with NSAID such as celecoxib (CCB) or dimethyl-CCB (DMC) in various type of human cancer cells. After ART treatment, the expression of p62, nuclear factor erythroid 2-like 2 (NRF2) and cancer stemness (CS)-related proteins including CD44, CD133, aldehyde dehydrogenase 1 (ALDH1), octamer-binding transcription factor 4 (Oct4), mutated p53 (mutp53) and c-Myc was down-regulated. ART induced autophagy as reduction of the autophagy receptor p62, which was associated with up-regulation of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and simultaneous down-regulation of NRF2 and CS-related proteins was occurred in the human cancer cells. These results indicate a possibility that ART activates autophagy through ATF4-CHOP cascade leading to down-regulation of CS-related proteins and subsequently eradicated cancer stem cells. In addition, co-treatment with ART and imatinib was more effective than either drug alone on growth inhibition and apoptosis induction of cancer cells. In conclusion, induction of autophagy-dependent cell death by ART might play a critical role in mediating the synergistic effect of drug combination (ART/NSAID and ART/imatinib). Therefore, ART could be a promising candidate as a chemosensitizer to enhance the anticancer effects of NSAID and imatinib.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1337-1342
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• 2004

The purpose of this research was to investigate the immunoregulatory effect and the leukemia cell apoptosis of EtOH extract of OGAPI(OGP). The proliferation of cultured splenocytes, thymocytes and mesenteric lymph node cells were enhanced by the addition of OGP. Splenic and thymic T lymphocytes, especially TH and Tc cells were significantly increased in OGP-administered mice. OGP markedly increased the production of γ-interferon in mice serum and accelerated the phagocytic activity in peritoneal macrophages. OGP treatment enhanced the apoptosis of L1210 mouse leukemia and Jurkat, Molt4 human leukemia cells, and increased the expression of apoptosis-related ICE, c-myc, p53 gene in Jurkat cell. These results suggest that OGP have an immunoregulatory action and anti-cancer activity.

• Natural Product Sciences
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• v.19 no.2
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• pp.155-159
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• 2013

Honokiol, a naturally occurring neolignan mainly found in Magnolia species, has exhibited a potential anti-proliferative activity in human cancer cells. However, the growth inhibitory activity against hepatocellular carcinoma cells and the underlying molecular mechanisms has been poorly determined. The present study was designed to examine the anti-proliferative effect of honokiol in SK-HEP-1 human hepatocellular cancer cells. Honokiol exerted anti-proliferative activity with cell-cycle arrest at the G0/G1 phase and sequential induction of apoptotic cell death. The cell-cycle arrest was well correlated with the down-regulation of checkpoint proteins including cyclin D1, cyclin A, cyclin E, CDK4, PCNA, retinoblastoma protein (Rb), and c-Myc. The increase of sub-G1 peak by the higher concentration of honokiol ($75{\mu}M$) was closely related to the induction of apoptosis, which was evidenced by decreased expression of Bcl-2, Bid, and caspase-9. Hohokiol was also found to attenuate the activation of signaling proteins in the Akt/mTOR and ERK pathways. These findings suggest that the anti-proliferative effect of honokiol was associated in part with the induction of cell-cycle arrest, apoptosis, and dow-nregulation of Akt/mTOR signaling pathways in human hepatocellular cancer cells.

• BMB Reports
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• v.55 no.9
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• pp.459-464
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• 2022

Various mechanisms have been suggested to explain the chemopreventive and tumor-inhibitory effects of melatonin. Despite the growing evidence supporting melatonin-induced mitochondrial dysfunction, it remains largely unknown how this phenomenon modulates metabolic reprogramming in cancer cells. The aim of our study was to identify the mechanism underlying the anti-proliferative and apoptotic effects of melatonin, which is known to inhibit glycolysis. We analyzed the time-dependent effects of melatonin on mitochondrial respiration and glycolysis in liver cancer cells. The results showed that from a cell bioenergetic point of view, melatonin caused an acute reduction in mitochondrial respiration, however, increased reactive oxygen species production, thereby inhibiting mTORC1 activity from an early stage post-treatment without affecting glycolysis. Nevertheless, administration of melatonin for a longer time reduced expression of c-Myc protein, thereby suppressing glycolysis via downregulation of HK2 and LDHA. The data presented herein suggest that melatonin suppresses mitochondrial respiration and glycolysis simultaneously in HCC cells, leading to anti-cancer effects. Thus, melatonin can be used as an adjuvant agent for therapy of liver cancer.

• Journal of Animal Reproduction and Biotechnology
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• v.38 no.4
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• pp.199-208
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• 2023

Background: Canine induced pluripotent stem cells (iPSCs) are an attractive source for veterinary regenerative medicine, disease modeling, and drug development. Here we used vitamin C (Vc) to improve the reprogramming efficiency of canine iPSCs, and its functions in the reprogramming process were elucidated. Methods: Retroviral transduction of Oct4, Sox2, Klf4, c-Myc (OSKM), and GFP was employed to induce reprogramming in canine fetal fibroblasts. Following transduction, the culture medium was subsequently replaced with ESC medium containing Vc to determine the effect on reprogramming activity. Results: The number of AP-positive iPSC colonies dramatically increased in culture conditions supplemented with Vc. Vc enhanced the efficacy of retrovirus transduction, which appears to be correlated with enhanced cell proliferation capacity. To confirm the characteristics of the Vc-treated iPSCs, the cells were cultured to passage 5, and pluripotency markers including Oct4, Sox2, Nanog, and Tra-1-60 were observed by immunocytochemistry. The expression of endogenous pluripotent genes (Oct4, Nanog, Rex1, and telomerase) were also verified by PCR. The complete silencing of exogenously transduced human OSKM factors was observed exclusively in canine iPSCs treated with Vc. Canine iPSCs treated with Vc are capable of forming embryoid bodies in vitro and have spontaneously differentiated into three germ layers. Conclusions: Our findings emphasize a straightforward method for enhancing the efficiency of canine iPSC generation and provide insight into the Vc effect on the reprogramming process.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.4
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• pp.436-441
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• 2009

In order to examine the effect of Injinhotang extract on the hepatocarcinogenesis induced by N-nitrosodiethylamine (NDEA) and carbon tetrachloride ($CCl_4$) in 8 week-old rats. Experimental rats were subdivided into three groups; normal group (Nor), hepatic cancer inducing control group (Con), and control group administered Injinhotang extract 260 mg/kg/day (IJH). The body weight decreased significantly (p<0.05) in the Con compared with the Nor. The body weight of IJH group more increased than Con. Rats intoxicated with NDEA had significantly (p<0.05) increased levels of serum AST, ALT, LDH, ALP, and AFP. On the contrary, group treated with Injinhotang extract had inhibited levels of serum AST, ALT, LDH, ALP, and AFP. The bcl-2 mRNA expression levels in rat liver were more increased in the IJH than Con, but these levels of c-myc mRNA were more decreased in the IJH than Con. Also, cytoplasmic vacuolizations in the liver of NDEA-administrated rats were inhibited by the treatment of Injinhotang extract. These results suggest that administration of Injinhotang extract suppresses or retards NDEA and $CCl_4$-induced hepatocarcinogenesis in rats.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.49 no.1
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• pp.75-85
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• 2023

This study was conducted to assess the effect of heptapeptide, composed of seven amino acids, on the activation of human hair cells isolated from human hair follicles. We have confirmed that the heptapeptide could bind to Lgr5 from the results of surface plasmon resonance (SPR) analysis. Heptapeptide enhanced the proliferation of human hair follicle dermal papilla cells (HHFDPCs) in a dose dependent manner. It induced the protein level of nuclear β-catenin, and the expressions of β-catenin downstream target genes, including LEF1, Cyc-D1 and c-Myc, in HHFDPCs. Heptapeptide significantly induced the phosphorylation of Akt and ERK, and the mRNA expressions of growth factors, including hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF), in HHFDPCs. In addition, heptapeptide significantly increased mRNA expression levels of differentiation-related transcription factors of human hair germinal matrix cells (HHGMCs) and differentiation markers of human hair outer root sheath cells (HHORSCs). Additionally, we investigated the effect of heptapeptide on human hair follicle stem cells (HHFSCs) differentiation and found that the heptapeptide reduced the mRNA and protein levels of stem cell markers, while it increased those levels of differentiation markers. These results have indicated that the heptapeptide promotes proliferation or differentiation of various types of hair follicle constituent cells through the induction of Wnt/β-catenin signaling. From the results, we have suggested that the heptapeptide in this study could be applied as a new functional material for the improvement of hair growth and alopecia.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5455-5461
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• 2012

Luteolin is a plant flavonoid which exhibits anti-oxidative, anti-inflammatory and anti-tumor effects. However, the antiproliferative potential of luteolin is not fully understood. In this study, we investigated the effect of luteolin on cell cycling and apoptosis in human esophageal squamous carcinoma cell line Eca109 cells. MTT assays showed that luteolin had obvious cytotoxicity on Eca109 with an $IC_{50}$ of $70.7{\pm}1.72{\mu}M$ at 24h. Luteolin arrested cell cycle progression in the G0/G1 phase and prevented entry into S phase in a dose- and time-dependent manner. as assessed by FCM. Luteolin induced apoptosis of Eca109 cells was demonstrated by AO/EB staining assay and annexin V-FITC/PI staining. Moreover, luteolin downregulated the expression of cyclin D1, survivin and c-myc, and it also upregulated the expression of p53, in line with the fact that luteolin was able to inhibit Eca109 cell proliferation.