• Journal of Haehwa Medicine
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• v.5 no.2
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• pp.523-533
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• 1997

Ursolic acid(UA) was isolated from Oldenlandiae diffusae Herba, one of the commonly used medicinal herbs for the treatment of cancer. IC50 of UA against cancer cell lines as SNU-1, B16-Fo. SK-OV3, HCT15, XF498, SK-MEL and A549 was $6{\mu}g/ml$, 4$4.4{\mu}g/ml$, $4.5{\mu}g/ml$, $4.6{\mu}g/ml$ and $4.2{\mu}g/ml$ respectively suggesting cytotoxicity against cancer cells. DNA fragmentation was expressed from the concnetration of $5.5{\mu}g/ml$ of UA by agarose electrphoresis. In the observation of morphological changes by phase contrast microscope, SEM and TEM, cell injury and condensation of cytoplasm from nucleus began 4 hr after UA treatment. fragmentaion of nucleus and injury of cell membrane was shown 24 hr after UA treatmeilt with SNU-1 cells. Aurin tricarboxic acid as endonuclease inhibitor. and nicotinamide as poly(ADP-ribose) polymerase inhibitor protected over 50% of cytotoxicity of UA against SNU-1 was at the concentrations of $3{\mu}M$ and $300{\mu}M$ respectively suggesting UA acts on nucleus. These results suggest that UA had antimetastatic effect and induced apoptosis.

• Biomedical Science Letters
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• v.26 no.2
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• pp.57-65
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• 2020

Excessive drinking of alcohol is known to be one of the main causes of various neurological diseases, such as Alzheimer's disease. Scopoletin is known to have anti-inflammatory and antioxidative properties, and to protect nerve cells. This study examined whether scopoletin inhibits the alcohol-induced apoptosis of primary hippocampal neurons, and how scopoletin regulates several factors associated with the caspase-mediated pathway. To achieve this, the cell viability and apoptosis rate of primary hippocampal neurons were measured by Cell Counting Kit-8 and flow cytometry, respectively. Apoptosis-related protein expressions (Bax, Bid, caspase-3, caspase-9, and Poly (ADP-ribose) polymerase (PARP)) were analyzed by Western blotting, and the ANOVA method was used to confirm the significance of the measured results. As a result, scopoletin inhibited the expressions of alcohol-induced apoptosis and apoptosis-related proteins in primary hippocampal neurons. These results suggest that down-regulation of Bid, Bax, and cleaved caspase-9 expression induced by scopoletin down-regulates the expression of cleaved caspase-3, inhibits the expression of cleaved PARP, and finally, inhibits mitochondrial apoptotic pathways. The study suggests that scopoletin is worth developing as a candidate for neuroprotective agent.

• BMB Reports
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• v.44 no.6
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• pp.381-386
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• 2011

In the present study, we characterized the function of HS1-binding protein 3 (HS1BP3), which is mutated in essential tremor and may be involved in lymphocyte activation. We found that HS1BP3 localized to the mitochondria and endoplasmic reticulum partially. Overexpression of HS1BP3 induced apoptosis in HEK293T and HeLa cell lines. When these cell lines were transfected with HS1BP3, they exhibited nuclear DNA condensation, externalization of phosphatidylserine (PS), and cleavage of poly ADP ribose polymerase (PARP). Furthermore, suppression of HS1BP3 or HS1 expression attenuates HS1BP3 induced apoptosis. In addition, HS1BP3 enhanced activator protein 1 (AP-1)-mediated transcription in a dose-dependent manner. Therefore, we conclude that HS1BP3 regulates apoptosis via HS1 and stimulates AP-1-mediated transcription.

• Journal of Ginseng Research
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• v.39 no.4
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• pp.299-303
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• 2015

Panax ginseng is a well-known economic medical plant that is widely used in Chinese traditional medicine. This species contains a unique class of natural products-ginsenosides. Recent clinical and experimental studies have presented numerous lines of evidence on the promising role of ginsenosides on different diseases including neurodegenerative diseases, cardiovascular diseases, and certain types of cancer. Nowadays, most of the attention has focused on ginsenoside Rd as a neuroprotective agent to attenuate ischemic stroke damages. Some of the evidence showed that ginsenoside Rd ameliorates ischemic stroke-induced damages through the suppression of oxidative stress and inflammation. Ginsenoside Rd can prolong neural cells' survival through the upregulation of the endogenous antioxidant system, phosphoinositide-3-kinase/AKT and extracellular signal-regulated protein kinase 1/2 pathways, preservation of mitochondrial membrane potential, suppression of the nuclear factor-kappa B, transient receptor potential melastatin, acid sensing ion channels 1a, poly(ADP-ribose) polymerase-1, protein tyrosine kinase activation, as well as reduction of cytochrome c-releasing and apoptosis-inducing factor. In the current work, we review the available reports on the promising role of ginsenoside Rd on ischemic stroke. We also discuss its chemistry, source, and the molecular mechanism underlying this effect.

• Archives of Pharmacal Research
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• v.26 no.5
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• pp.405-410
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• 2003

Vitamin K-related analogs induce growth inhibition in various cancer cell lines. A naphthoquinone analog, termed 2,3-dichloro-5, 8-dihydroxy-1,4-naphthoquinone (DDN), induces apoptosis in human promyeloid leukemic HL-60 cells, and shows antitumor activity in vivo. Following treatment with DDN, evidence of apoptosis, including DNA fragmentation and cleavage of poly ADP ribose polymerase (PARP), was observed. DDN induced an upregulation of proapoptotic Bax protein, and Bid cleavage. Antiapoptotic Bcl-2 protein levels were not changed by DDN, but the expression of Bcl-xL was decreased. In addition, DDN reduced the mass of solid tumor in the Sarcoma 180 tumor-bearing mouse model. These results indicate that DDN exerts antitumor activity, which appears to be related to the induction of apoptosis by regulating Bcl-2 family proteins.

• Animal cells and systems
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• v.15 no.1
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• pp.1-8
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• 2011

Perturbation of metabolism with increased expression of lipogenic enzymes is a common characteristic of human cancers, including prostate cancer. In the present work the overexpression of stearoyl-CoA desaturase (SCD) in LNCaP cells led to increased mRNA levels of fatty acid synthase (FAS) and acetyl-CoA-carboxylase-a, whereas micro RNA-mediated silencing of SCD inhibited the expression of these lipogenic genes in LNCaP cells. Treatment with the FAS-specific inhibitor cerulenin inhibited SCD induction of LNCaP cell proliferation. In addition, a transient transfection assay revealed the capability of cerulenin to suppress SCD and dihydrotestosterone induction of androgen receptor transcriptional activity. Furthermore, overexpression of SCD in LNCaP cells produced marked resistance to ceramide-induced cell death with reduced poly(ADP-ribose) polymerase (PARP) cleavage. In contrast, silencing of SCD expression increased Bax protein in LNCaP cells. Furthermore, addition of ceramide to SCD knockdown LNCaP cells increased cell death and caspase-3 activity with drastic increase of PARP cleavage. Together, the data indicate that SCD may provide resistance of prostate cancer cells to ceramide-induced cell death.

• Archives of Pharmacal Research
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• v.24 no.4
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• pp.342-348
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• 2001

In a course of obtaining more amount of bioactive costunolide and successive phytochemical isolation from Magnolia sieboldii (Magnoliaceae), a novel acyclic monoterpene 1 named deoxygeraniol (2,6(E)-dimethyl-2,6-octadiene) was isolated along with $\beta$-sitosterol 3-O-linoleate (2), trilinolein (3) and high amount of costunolide (4) in the pure state. The structure of compound 1 was determined on the basis of spectroscopic data. Costunolide was found to induce apoptotic cell death in a dose-dependent manner by nucleosomal DNA ladder and flow cytometric analysis. Immunoblot analysis showed that the level of the anti-apoptotic protein, Bcl-2, was decreased, whereas the cleavage of poly-(ADP-ribose) polymerase was, activated furthermore, the N-acetyl-L-cysteine antioxidant effectively prevented costunolide-induced cytotoxicity. These results suggest that costunolide-induced cell death is mediated by reactive oxygen species.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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• pp.1423-1430
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• 2009

Rosmarinic acid frequently found as a secondary metabolite in herbs and medicinal plants, has exhibited antimicrobial, antiviral, antioxidative, and anti-inflammatory activities. The proliferation and migration of human aortic smooth muscle cells (HASMC) in response to activation by various stimuli plays a critical role in the initiation and development of atherosclerosis. This study was conducted to examine the effects of Rosmarinic acid on the proliferation and migration of HASMC. Rosmarinic acid suppressed the proliferation of HASMC via induction of the expression of apoptotic proteins including cleaved poly ADP-ribose polymerase (PARP), and caspase-3. Rosmarinic acid decreased anti-apoptotic Bcl-2 and increased pro-apoptotic Bax. Moreover, treatment of rosmarinic acid decreased the G1/S cycle regulation proteins (cyclin D1, cyclin E, CDK2, CDK4 and CDK6) and increased p21, p27 and p53. Rosmarinic acid also blocked HASMC migration via suppression of MMP-9 and MMP-2. Taken together, these results indicate that rosmarinic acid has the potential for use as an anti-atherosclerosis agent.

• The Journal of Internal Korean Medicine
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• v.22 no.2
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• pp.183-191
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• 2001

신경교세포에서 황금추출물이 반응성 산소기에 의한 세포 사망을 방지할 수 있는지를 확인하기 위하여 사람의 glioama 세포주인 A172 세포를 사용하여 $H_2O_2$의 독성작용에 대한 영향을 조사하였다. 세포 사망 정도는 tryptan blue exclusion과 MTT reduction assay로 평가하였다. $H_2O_2$는 세포 사망을 유도하였으며 또한 세포내 ATP 함량을 감소시켰으며, 이러한 효과는 황금 추출물에 의해 방지되었으며 그 효과는 농도 의존적으로 나타났다. $H_2O_2$에 의한 세포 사망은 잘 알려진 flavonoid인 quercetin과 철착염제인 phenanthroline에 의해 방지되었으나, 항산화제인 DPPD나 Trolox에 의해서는 영향을 받지 않았다. $H_2O_2$는 poly (ADP-ribose) polymerase를 활성화시켰으며, 이러한 효과는 황금, quercetin 및 phenanthroline에 의해 억제되었다. 황금 추출물은 유기산화제인 t-buthyhydroperoxide 및 중금속인 수은에 의한 세포 사망을 방지하였다. 이러한 실험 결과는 황금 추출물이 $H_2O_2$에 의한 세포 사망을 방지하며 그 효과는 황금의 flavonoid 성분이 철과 결합하여 $H_2O_2$로부터 hydroxy radical의 생성을 억제함으로써 나타나는 것으로 추측된다.

• Food Science and Biotechnology
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• v.15 no.4
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• pp.534-542
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• 2006

The effects of ethanol fractions of three different rice grain extracts, Jakwangchalbyeo, Hwasunchalbyeo, and Ilpumbyeo, on apoptotic cell death in the rat hepatoma H4IIE cell line were investigated using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cell viability assay. One hundred mg/mL Jakwangchalbyeo extract significantly reduced cell viability to 69.5, 57.2, and 46.1% within 24, 48, and 72 hr, respectively. Fluorescence-activated cell sorting (FACS) analyses were also performed to characterize the cell death pattern caused by treatment with the rice grain extracts. Apoptotic cell death was clearly observed with time after treatment with the Jakwangchalbyeo extract. In Western blotting analysis, degradation of the 116 kDa poly-ADP-ribose polymerase (PARP) molecule was observed with concomitant formation of an 89 kDa product 24, 48, and 72 hr after treating cells with the Jakwangchalbyeo extract. This indicates that an apoptotic process caused cell death in these cells. In conclusion, red-pericarp Jakwangchalbyeo extract induced apoptotic cell death in H4IIE cells to a larger extent than the other rice extracts.