Kyung Song

Wonkwang University, Riri, Jeollabuk-do, South Korea

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Publications (9)27.65 Total impact

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    ABSTRACT: Leptin, a hormone mainly produced from adipose tissue, has been shown to induce proliferation of cancer cells. However, the molecular mechanisms underlying leptin-induced tumor progression have not been clearly elucidated. In the present study, we investigated the role of autophagy in leptin-induced cancer cell proliferation using human hepatoma (HepG2) and breast cancer cells (MCF-7), and tumor growth in a xenograft model. Herein, we showed that leptin treatment caused autophagy induction as assessed by increase in expression of autophagy-related genes, including beclin-1, Atg5 and LC3 II, further induction of autophagosome formation and autophagic flux. Interestingly, inhibition of autophagic process by treatment with inhibitors and LC3B gene silencing blocked leptin-induced increase in cell number and suppression of apoptosis, indicating a crucial role of autophagy in leptin-induced tumor progression. Moreover, gene silencing of p53 or FoxO3A prevented leptin-induced LC3 II protein expression, suggesting an involvement of p53/FoxO3A axis in leptin-induced autophagy activation. Leptin administration also accelerated tumor growth in BALB/c nude mice, which was found to be autophagy dependent. Taken together, our results demonstrate that leptin-induced tumor growth is mediated by autophagy induction and autophagic process would be a promising target to regulate development of cancer caused by leptin production.
    Oncotarget 01/2015; · 6.63 Impact Factor
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    ABSTRACT: Baicalein, a flavonoid and aglycon hydrolyzed from baicalin, has anticancer properties in several human cancers, but its molecular mechanisms of action remain unclear. Here, we showed that baicalein leads to human cancer cell death by inducing autophagy rather than apoptosis, since cell death induced by baicalein was completely reversed by suppressing the expression levels of key molecules in autophagy such as beclin1, Vps34, Atg5 and Atg7, but not by pan-caspase inhibitor. Our data revealed that baicalein significantly increased the number of green fluorescence protein-cytosol-associated protein light chain 3 (GFP-LC3)-containing puncta and LC3B-II expression levels, which were further enhanced by chloroquine treatment. Furthermore, a luciferase-based reporter assay showed that the ratio of RLuc-LC3wt/RLuc-LC3G120A was greatly reduced. These data suggested that baicalein induced not only autophagosome formation, but also autophagic flux. Experiments using short interfering RNAs and pharmacological inhibitors revealed that Beclin 1, vacuolar protein sorting 34 (Vps34), Atg5, Atg7, and ULK1 play pivotal roles in mediating baicalein-induced autophagy. Moreover, baicalein activated AMPKα, leading to ULK1 activation through phosphorylation at Ser555, while both protein and mRNA levels of mammalian target of rapamycin (mTOR) and Raptor, upstream inhibitors of ULK1 and autophagy, were markedly downregulated by baicalein. Our data suggest that the anticancer effects of baicalein are mainly due to autophagic cell death through activation of the AMPK/ULK1 pathway, and inhibition of mTOR/Raptor complex 1 expression. These results provide new mechanistic insights into the anticancer functions of autophagy inducers, such as baicalein, which may be used as potential therapeutics for cancer treatment.This article is protected by copyright. All rights reserved.
    FEBS Journal 08/2014; 281(20). DOI:10.1111/febs.12969 · 3.99 Impact Factor
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    ABSTRACT: Globular adiponectin (gAcrp) protects liver cells from ethanol-induced apoptosis via induction of autophagy. However, the underlying mechanisms are unknown. The present study aims to investigate the potential role of autophagy-related protein 5 (Atg5), an essential Atg for the elongation of autophagosomes, in suppression of ethanol-induced cytotoxicity by gAcrp. Here, we demonstrated that suppression of Atg5 expression by ethanol was restored by pretreatment with gAcrp both in primary rat hepatocytes and human hepatoma cell line (HepG2). Moreover, ethanol-induced accumulation of p62 (sequestosome1), a marker of autophagic flux, was restored by gAcrp treatment, implying that gAcrp modulates autophagic flux in liver cells. Further, Atg5 silencing prevented p62 degradation by gAcrp, suggesting that Atg5 plays a critical role in induction of autophagic flux by gAcrp. Interestingly, gene silencing of Atg5 by siRNA abrogated restoration of autophagosome formation by gAcrp in ethanol-treated cells. Finally, protection of liver cells by gAcrp from ethanol-induced apoptosis was also significantly attenuated by knocking-down of Atg5 expression, suggesting an important role of Atg5 in autophagy induction and cellular apoptosis modulated by gAcrp. Taken together, our data demonstrated that Atg5 expression, at least in part, is implicated in gAcrp-induced autophagy and subsequent anti-apoptotic effects in ethanol-treated liver cells.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 02/2014; 68. DOI:10.1016/j.fct.2014.02.027 · 2.61 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the effects of Opuntia humifusa (OH) on cerulein-induced acute pancreatitis (AP). Acute pancreatitis was induced via intraperitoneal injection of cholecystokinin analog cerulein (50 μg/kg). In the OH pretreatment group, OH was administered intraperitoneally (100, 250, or 500 mg/kg) 1 hour before first cerulein injection. In the posttreatment group, OH was administered intraperitoneally (500 mg/kg) 1 hour after the first cerulein injection. Furthermore, we isolated the pancreatic acinar cells using collagenase method, then investigated the acinar cell viability, cytokine productions, and the regulating mechanisms. The both pretreatment and posttreatment of OH treatment attenuated the severity of AP, as shown by the histology of the pancreas and lung, and inhibited neutrophil infiltration; serum amylase and lipase activities; proinflammatory cytokine expression such as interleukin 1, interleukin 6, and tumor necrosis factor α; and cell death including apoptosis and necrosis. Furthermore, OH inhibited the activation of c-Jun N-terminal kinases. These results suggest that OH reduces the severity of AP by inhibiting acinar cell death through c-Jun N-terminal kinases.
    Pancreas 01/2014; 43(1):118-27. DOI:10.1097/MPA.0b013e318296f903 · 3.01 Impact Factor
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    ABSTRACT: MicroRNA-21 and programmed cell death 4 (PDCD4), a downstream target of miR-21, mediate diverse physiological responses. Here we demonstrate that globular adiponectin (gAcrp) modulates expression of miR-21 and PDCD4 in RAW 264.7 macrophages. These effects were abrogated by inhibitors of ERK1/2, JNK or NF-κB. Conditioned media collected from gAcrp-stimulated RAW 264.7 macrophages caused similar effects as direct gAcrp treatment, showing the paracrine effect of gAcrp. These data indicate that gAcrp modulates the miR-21/PDCD4 axis through the ERK and JNK/NF-κB pathways in RAW 264.7 macrophages and further suggest that the miR-21/PDCD4 axis may be a novel target mediating adiponectin-induced biological responses.
    FEBS letters 04/2013; 587(10). DOI:10.1016/j.febslet.2013.03.040 · 3.34 Impact Factor
  • Sunhyo Kim, Eun-Jung Jin, Kyung Song
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    ABSTRACT: Sulfuretin (3',4',6'-trihydroxyaurone), one of the key flavonoids isolated from Rhus verniciflua, is known to suppress inflammation and oxidative stress. However, the anti-cancer properties of sulfuretin as well as its mechanism of action remain poorly understood. Here, we show that the expression of miR-30C is markedly enhanced in sulfuretin-stimulated cells, consequently promoting apoptosis and cell cycle arrest in human cancer cell lines. The transient transfection of pre-miR-30C resulted in greater than 70% growth inhibition in PC-3 cells and provided strong evidence that miR-30C selectively suppresses the expression of cyclin D1 and D2, but not cyclin D3. Target validation analysis revealed that 3'-UTR of cyclin D2 is a direct target of miR-30C, whereas suppression by miR-30C of cyclin D1 may occur through indirect mRNA regulation. In addition, silencing miR-30C expression partially reversed sulfuretin-induced cell death. Taken together, our data suggest that miR-30C, a tumor suppressor miRNA, contributes to anti-cancer properties of sulfuretin by negatively regulating cyclin D1 and D2, providing important implications of sulfuretin and miR-30C for the therapeutic intervention of human cancers.
    Biochemical and Biophysical Research Communications 01/2013; 431(3). DOI:10.1016/j.bbrc.2013.01.012 · 2.28 Impact Factor
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    ABSTRACT: Acute pancreatitis (AP) is a complicated inflammatory disease that has an unknown underlying pathogenesis. Because alpha-pinene can modulate inflammation, we examined whether alpha-pinene plays a role in AP. Alpha-pinene was administered intraperitoneally 1h prior to the first injection of cerulein. Once AP developed, cerulein, a stable cholecystokinin analog, was injected hourly over a 6-h period. Blood samples were taken 6h later to determine serum amylase and lipase levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. We also isolated the pancreatic acinar cells using a collagenase solution. Cell viability, and cytokine productions were measured in pancreatic acini. Intraperitoneal administration of alpha-pinene reduced the pancreatic weight (PW) to body weight (BW) ratio and the serum levels of amylase and lipase. Alpha-pinene treatment also reduced histological damage and myeloperoxidase activity in the pancreas and lungs. Furthermore, alpha-pinene pretreatment reduced the production of pancreatic tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 during cerulein-induced AP. In vitro, alpha-pinene inhibited cerulein-induced cell death and cytokine production in isolated cerulein-treated pancreatic acinar cells. These findings suggest that alpha-pinene has an anti-inflammatory effect during cerulein-induced AP.
    Life sciences 09/2012; 91(17-18):866-71. DOI:10.1016/j.lfs.2012.08.035 · 2.30 Impact Factor
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    ABSTRACT: Antisense oligonucleotide represents an interesting tool for selective inhibition of gene expression. However, their low efficiency of introduction within intact cells remains to be overcome. Antisense-TGFbeta (25 mer) and antisense-TNFalpha (18 mer) were used to study the cellular transport and biological function of antisense oligonucleotide in vitro. Since TGF and TNF play on important role in regulating the nitric oxide production from macrophages, the action of the above antisense oligonucleotides was easily monitored by the determination of nitrite. Poly-L-lysine, benzalkonium chloride and tetraphenylphosphonium chloride were used as polycations, which neutralize the negative charge of antisense oligonucleotide. The production of nitric oxide mediated by gamma-IFN in mouse peritoneal macrophage was increased by antisense-TGFbeta in a dose-dependent manner. Antisense-TNFalpha reduced the nitric oxide release from activated RAW 264.7 cells. Significant enhancement in the nitric oxide production was investigated by the cotreatment of poly-L-lysine with antisense-TGFbeta. On the meanwhile, inhibition effect of antisense-TNFalpha is not changed by the addition of poly-L-lysine. These results demonstrate that control of expression of TGFbeta and TNFalpha gene is achieved using antisense technology and the cellular uptake of antisense oligonucleotide could be enhanced by ion-pairing.
    Archives of Pharmacal Research 11/1997; 20(5):438-42. DOI:10.1007/BF02973936 · 1.75 Impact Factor
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    ABSTRACT: Antisense oligonucleotides seem to provide a promising new tool for the therapy. Choiet al. (1995) reported antisense phosphorothioate oligonucleotides (PS-ODN, 25 mer) complementary to TGF-β mRNA designed for scar formation inhibitor to eliminate scars, which was caused by undesired collagen deposition due to overexpression of TGF-β, in wounded skin. PS-ODN were evaluatedin vitro for skin penetration using normal and tape-stripped damaged rat skin. Thein vitro skin transports were carried out with partially modified PS-ODN (6S) and fully modified PS-ODN (25S). The cumulative amount of PS-ODN (6S) penetrated through normal rat skin was 0.234±0.041 μg/cm2 and that of tape-stripped damaged rat skin was 1.077±0.301 μg/cm2 over 8 hrs. PS-ODN (25S) can not be found in receptor medium through normal skin due to high molecular weight (Mol.Wt.=8,000) and polyanionic charge. However, the cumulative amount of PS-ODN (25S) penetrated across damaged rat skin in PBS was 0.340±0.296 μg/cm2 over 8 hrs. The absense of dermis raised the cumulative amount of PS-ODN (6S) penetrated through rat skin. And the fluxes of PS-ODN (6S) and PS-ODN (25S) at 8hrs across damaged rat skin were 134.63±37.67 ng/cm2 h, and 42.50±36.95 ng/cm2 h, respectively. While PS-ODN (25S) was stable in 10% heat inactivated fetal bovine serum (FBS) during 24 hrs, PS-ODN (6S) was less stable than PS-ODN (25S), but was markedly stable than unmodified phosphodiester. It is suggested that the cumulative amount of PS-ODN (6S) penetrated through damaged rat skin is larger than that of PS-ODN (25S) since the former is easier to degrade by nuclease than the latter and then is apt to penetrate into skin. Thus, PS-ODN represents a logical candidate for further evaluation due to the potential for delivery into the wounded skin.
    Archives of Pharmacal Research 04/1996; 19(2):116-121. DOI:10.1007/BF02976845 · 1.75 Impact Factor