• Journal of Food Hygiene and Safety
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• v.34 no.5
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• pp.495-501
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• 2019

Aloin [1,8-Dihydroxy-10-(${\beta}$-D-glucopyranosyl)-3-(hydroxymethyl)-9(10H)-anthracenone], is a natural anthraquinone from aloe. It has been shown to have antioxidant and anticancer effects in various types of human cancer cells, but the anticancer effects of aloin in human colorectal cancer cells HT-29 have not been elucidated. In this study, possible mechanisms by which aloin exerts its apoptotic action in cultured human colorectal cancer HT-29 cells were investigated. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay shows that treatment with aloin (0, 100, 200, 300 and $400{\mu}M$) reduced cell viability in a concentration-dependent manner in HT-29 and showed no effects on cell proliferation in A375SM and AGS cells. In addition, it was confirmed that apoptotic body was significantly increased as shown by 4',6-diamidino-2-phenylindole (DAPI) staining, and increased apoptosis rate by flow cytometry in HT-29 cells treated with aloin (0, 200 and $400{\mu}M$). We confirmed by western blotting that aloin activated Bax (pro-apoptotic), cleaved-poly (ADP-ribose) polymerase (PARP) and caspase-3, -8 and Bcl-2 (anti-apoptotic) were not changed compared with the control. Aloin induced up-regulation of phospho-p38 and down-regulation of phospho-extracellular signal-regulated kinase (ERK)1/2. Therefore, aloin suppressed the growth inhibitory effects by the induction of apoptosis in human colorectal cancer cells and has potential as a cancer preventive medicine.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9915-9919
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• 2014

Lamellarin D (LamD) is a marine alkaloid with a pronounced cytotoxicity against a large panel of cancer cells, affecting cell growth and inducing apoptosis. However, the molecular mechanisms of action of this compound are poorly understood. In this study, the anticancer efficacy of LamD was investigated in human leukemia K562 cells. The results showed suppressed cell proliferation and induction of G0/G1-phase arrest,while expression of CDK1, and activity of smad3 and smad5 were reduced, but that of p27, p53 and STGC3 was increased. LamD induced cell apoptosis through activation of caspases-8/-3, inhibition of survivin and Bcl-2, suggesting that this compound may also act through a caspase-independent pathway. Moreover, LamD inhibited the secretion of TGF-${\beta}$, IL-$1{\beta}$, IL-6, IL-8 and other inflammatory cytokines and the transcriptional activity of transcription factor NF-${\kappa}B$ in human leukemia K562 cells.Taken together, our results suggest that LamD-mediated inhibition of leukemia cell proliferation may be related to the induction of apoptosis and the regulation of cell cycle, tumor-related gene expression and cytokine expression, which may provide a new way of thinking for the treatment leukemia.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9445-9451
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• 2014

Neuroblastoma is the most common extracranial solid tumor in children. Approximately half of the affected patients are diagnosed with high-risk poor prognosis disease, and novel therapies are needed. Sanguinarine is a benzophenanthridine alkaloid which has anti-microbial, anti-oxidant and anti-inflammatory properties. The aim of this study is whether sanguinarine has in vitro apoptotic effects and which apoptotic genes might be affected in the human neuroblastoma cell lines SH-SY5Y (N-myc negative), Kelly (N-myc positive, ALK positive), and SK-N-BE(2). Cell viability was analysed with WST-1 and apoptotic cell death rates were determined using TUNEL. After RNA isolation and cDNA conversion, expression of 84 custom array genes of apoptosis was determined. Sanguinarine caused cell death in a dose dependent manner in all neuroblastoma cell lines except SK-N-BE(2) with rates of 18% in SH-SY5Y and 21% in Kelly human neuroblastoma cells. Cisplatin caused similar apoptotic cell death rates of 16% in SH-SY5Y and 23% in Kelly cells and sanguinarine-cisplatin combinations caused the same rates (18% and 20%). Sanguinarine treatment did not affect apoptototic gene expression but decreased levels of anti-apoptotic genes NOL3 and BCL2L2 in SH-SY5Y cells. Caspase and TNF related gene expression was affected by the sanguinarine-cisplatin combination in SH-SY5Y cells. The expression of regulation of apoptotic genes were increased with sanguinarine treatment in Kelly cells. From these results, we conclude that sanguinarine is a candidate agent against neuroblastoma.

• Journal of Pharmacopuncture
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• v.17 no.2
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• pp.7-17
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• 2014

Objectives: Condurango is widely used in various systems of complementary and alternative medicines (CAM) against oesophageal and stomach ailments including certain types of cancer. However, until now no systematic study has been conducted to verify its efficacy and dose with proper experimental support. Therefore, we examined if ethanolic extract of Condurango could ameliorate benzo[a]pyrene (BaP)-induced lung cancer in rats, in vivo to validate its use as traditional medicine. Methods: Fifteen male and 15 female Sprague-Dawley (SD) rats were treated with 0.28 mg/kg of Sweet Bee Venom (SBV) (high-dosage group) and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group) for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results: A histological study revealed gradual progress in lung tissue-repair activity in Condurango-fed cancer-bearing rats, showing gradual tissue recovery after three months of drug administration. Condurango has the capacity to generate reactive oxygen species (ROS), which may contribute to a reduction in anti-oxidative activity and to an induction of oxidative stress-mediated cancer cell-death. Condurango-activated pro-apoptotic genes (Bax, caspase-3, caspase-9, p53, cytochrome-c, apaf-1, ICAD and PARP) and down-regulated antiapoptotic-Bcl-2 expression were noted both at mRNA and protein levels. Studies on caspase-3 activation and PARP cleavage by western blot analysis revealed that Condurango induced apoptosis through a caspase-3-dependent pathway. Conclusion: The anticancer efficacy of an ethanolic extract of Condurango for treating BaP-induced lung cancer in rats lends support for its use in various traditional systems of medicine.

• Journal of Life Science
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• v.23 no.6
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• pp.812-824
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• 2013

Reserpine, an anti-hypertensive drug, is able to positively modulate several phenotypes associated with $A{\beta}$ toxicity in a Caenorhabditis elegans model of Alzheimer's disease (AD). We investigated into the therapeutic effects of reserpine on mammalian neurodegenerative disorders, and found that significant alteration of the key factors influencing AD was detected in Tg2576 mice after reserpine treatment for 30 days. The aggressive behavior of Tg2576 mice was significantly improved upon reserpine treatment, whereas their social contact was consistently maintained. Furthermore, the levels of $A{\beta}$-42 peptide in the hippocampus of the brain and blood serum were lower in the reserpine-treated group than in the vehicle-treated group. Among g-secretase components, the expression levels of PS-2, Pen-2, and APH-1 were slightly lower in reserpine-treated Tg2576 mice, although a significant change in nicastrin (NCT) expression was not detected. Furthermore, the serum level of nerve growth factor (NGF) increased in reserpine-treated Tg2576 mice compared with vehicle-treated mice. Among down-stream effectors of the NGF receptor TrkA signaling pathway, reserpine treatment induced elevation of TrkA phosphorylation and reduction of ERK phosphorylation. In addition, in the NGF receptor $p75^{NTR}$ signaling pathway, the expression levels of $p75^{NTR}$ and Bcl-2 were enhanced in reserpine-treated Tg2576 mice compared with vehicle-treated mice, whereas the expression level of RhoA declined. Overall, these results suggest that reserpine can help relieve AD pathogenesis in Tg2576 mice through downregulation of $A{\beta}$-42 deposition, alteration of ${\gamma}$-secretase components, and regulation of NGF metabolism.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.8
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• pp.1095-1101
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• 2016

Ginsenoside Rg1 is a natural compound with various efficacies and functions. It has beneficial effects on aging, diabetes, and immunity, as well as antioxidant and proliferative functions. However, its effect on porcine embryo development remains unknown. We investigated the effect of ginsenoside Rg1 on the in vitro development of preimplantation porcine embryos after parthenogenetic activation in high-oxygen conditions. Ginsenoside treatment did not affect cleavage or blastocyst formation rates, but did increase the total cell number and reduced the rate of apoptosis. In addition, it had no effect on the expression of four apoptosis-related genes (Bcl-2 homologous antagonist/killer, B-cell lymphoma-extra large, Caspase 3, and tumor protein p53) or two metabolism-related genes (mechanistic target of rapamycin, carnitine palmitoyltransferase 1B), but increased the expression of Glucose transporter 1 (GLUT1), indicating that it may increase glucose uptake. In summary, treatment with the appropriate concentration of ginsenoside Rg1 ($20{\mu}g/mL$) can increase glucose uptake, thereby improving the quality of embryos grown in high-oxygen conditions.

• Journal of Embryo Transfer
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• v.31 no.3
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• pp.169-177
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• 2016

There is a growing interest in the application of primary hepatocytes for treatment of liver diseases in humans and for drug development. Several studies have focused on long-term survival and di-differentiation blocking of primary hepatocytes in an in vitro culture system. Therefore, the present study also aimed to optimize an in vitro culture system using primary rat hepatocytes. Primary rat hepatocytes from 6-week-old male Crl:CD rats were isolated using a modified two-step collagenase perfusion. Healthy $3.5{\times}10^6$ primary rat hepatocytes were seeded into a 2 dimensional (2D) culture in a 25T culture flask coated with collagen type I or into a 3D culture in a 125-ml spinner flask for 7 days. Production of plasma protein (ALB and TF), apoptosis (BAX and BCL2), and CYP (CYP3A1) related genes were compared between the 2D and 3D culture systems. The 3D culture system had an advantage over the 2D system because of the relatively high expression of ALB and low expression of BAX in the 3D system. However, the level of CYP3A1 did not improve in the 3D culture with and without the presence of a dexamethasone inducer. Therefore, 3D culture has an advantage for albumin production and primary rat hepatocyte survivability, but a low expression of CYP3A1 indicated that primary rat hepatocytes require a high-density culture for stress reduction by continuous flow.

• Journal of Life Science
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• v.29 no.10
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• pp.1062-1070
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• 2019

A components of garlic (Allium sativum) have anti-proliferative effects against various types of cancer. We aimed to investigate the capacity of garlic compounds to anti-tumor on a various cancer cell lines. Fractionation of garlic extract, guided by antiproliferative activity against human gastric cancer (AGS) cells, has resulted in the isolation of N-benzyl-N-methyldecan-1-amine (NBNMA). We investigated the effect of newly isolated NBNMA from garlic cloves on the inhibition of the growth of CT-26, AGS, HepG2, HCT-116, MCF7, B16F10, and Sarcoma-180 cells for in vitro and CT-26 colon carcinoma cells in vivo. NBNMA exhibited an antiproliferative effect in CT-26 cells by apoptotic cell death. NBNMA exhibited down-regulation of anti-apoptotic Bcl-2 proteins and up-regulation of apoptotic Bad protein expression in western blot analyses. In addition, NBNMA meagre activated caspase 3 and caspase 9, initiator caspases of the extrinsic and intrinsic pathways of apoptosis. NBNMA treatment at a dose of 10 mg/kg for 21 days in experimental mice implanted with tumors resulted in significant reduction of the tumor weight (43%). NBNMA exhibited both in vitro and in vivo anticancer activity. These results indicate that NBNMA has promising potential to become a novel anticancer agent from garlic cloves for the treatment of colon carcinoma cancer.

• Proceedings of the Korean Vacuum Society Conference
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• 2011.08a
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• pp.266-267
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• 2011

질화갈륨(GaN)은 높은 전자이동도 및 높은 항복전계를 가지며 낮은 온저항으로 인하여 에너지효율이 우수하기 때문에 고출력 전력소자 분야에서 많은 관심을 받고 있다. GaN을 이용한 고출력 전력소자의 경우 상용화 수준에 근접할 만한 기술적 진보가 있었으나, 페르미 레벨 고정(Fermi-level pinning) 현상, 소자의 누설전류 등 아직 해결되어야 할 문제를 갖고 있다. 본 연구에서는 실리콘 기판 위에 성장된 GaN 에피탁시를 활용한 고출력 전력소자의 누설전류를 억제시키기 위해 오믹 접합 중 Au의 상호확산을 억제하는 중간층 금속(Mo or Ni)을 변화시켰으며 오믹 열처리 온도에 따른 특성을 비교 연구하였다. $Cl_2$와 $BCl_3$를 이용하여 0.6 ${\mu}m$ 깊이의 메사 구조가 활성영역을 형성하였고, Si 도핑된 n-GaN 위에 Ti/Al/Mo/Au (20/100/25/200 nm) 와 Ti/Al/Ni/Au (20/100/25/200 nm) 오믹 접합을 각각 설계, 제작하였다. 오믹 열처리시의 GaN 표면오염을 방지하기 위해 $SiO_2$ 희생층을 증착하였다. 오믹 접합 형성을 위해 각 750$^{\circ}C$, 800$^{\circ}C$, 850$^{\circ}C$에서 30초간 열처리를 진행 하였으며, 이후 6 : 1 BOE 용액으로 $SiO_2$ 희생층을 제거하였다. 750, 800, 850$^{\circ}C$에서 Ti/Al/Mo/Au 구조의 오믹 접합 저항은 각 2.56, 2.34, 2.22 ${\Omega}$-mm 이었으며, Ti/Al/Ni/Au 구조의 오믹 접합 저항은 각 43.72, 2.64, 1.86 ${\Omega}$-mm이었다. Isolation 누설전류를 측정하기 위해서 두 개의 오믹 접합 사이에 메사 구조가 있는 테스트 구조를 제안하였다. Isolation 누설전류는 Ti/Al/Mo/Au 구조에서 두 오믹 접합 사이의 거리가 25 ${\mu}m$이고 100 V일 때 750, 800, 850 $^{\circ}C$의 열처리 온도에서 각 1.25 nA/${\mu}m$, 2.48 nA/${\mu}m$, 8.76 nA/${\mu}m$이었으며, Ti/Al/Ni/Au 구조에서는 각 1.58 nA/${\mu}m$, 2.13 nA/${\mu}m$, 96.36 nA/${\mu}m$이었다. 열처리 온도가 증가하며 오믹 접합 저항은 감소하였으나 isolation 누설전류는 증가하였다. 750$^{\circ}C$ 열처리에서 오믹 접합 저항은Ti/Al/Mo/Au 구조가 Ti/Al/Ni/Au 구조보다 약 17배 우수하였고, 850$^{\circ}C$ 고온의 열처리 경우 Ti/Al/Mo/Au 구조의 isolation 누설전류는 8.76 nA/${\mu}m$로 Ti/Al/Ni/Au의 누설전류 96.36 nA/${\mu}m$보다 약 11배 우수하였다. Ti/Al/Mo/Au가 Ti/Al/Ni/Au 보다 오믹 접합 저항과 isolation 누설전류 측면에서 전력용 GaN 소자에 적합함을 확인하였다.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2525-2528
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• 2013

The Homer protein family, also known as the family of cytoplasmic scaffolding proteins, which include three subtypes (Homer1, Homer2, Homer3). Homer3 can regulate transcription and play a very important role in the differentiation and development for some tissues (e.g. muscle and nervous systems). The current studies showed that Homer3 abnormal expression changes in acute myeloid leukemia (AML). Forced expression of Homer3 in transfected K562 cells inhibited proliferation, influenced the cell cycle profile, affected apoptosis induced by $As_2O_3$ through inhibition of Bcl2 expression, and also promoted cell differentiation induced by 12-O-tetra decanoylphorbol-acetate (TPA). These results showed that Homer3 is a novel gene which plays a certain role in the occurrence and development of AML.