• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3131-3138
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• 2016

Several studies have addressed the possible role of hepatitis C virus genotype-4 (HCV GT4) in apoptosis. However, this still not fully understood. In the current study a re-constructed clone of E1/E2 polyprotein region of the HCV GT4 was transfected into the Huh7 cell line and a human apoptotic PCR array of 84 genes was used to investigate its possible significance for apoptosis. Out of the 84 genes, only 35 showed significant differential expression, 12 genes being up-regulated and 23 down-regulated. The highest-up regulated genes were APAF1 (apoptotic peptidase-activating factor 1), BID (BH3 interacting domain death agonist) and BCL 10 (B-cell CLL/lymphoma protein 10) with fold regulation of 33.2, 30.1 and 18.9, respectively. The most down-regulated were FAS (TNF receptor super family), TNFRSF10B (tumor necrosis factor receptor super-family member 10b) and FADD (FAS-associated death domain) with fold regulation of -30.2, -27.7 and -14.9, respectively. These results suggest that the E1/E2 proteins may be involved in HCV-induced pathogenesis by modulating apoptosis through the induction of the intrinsic apoptosis pathway and disruption of the BCL2 gene family.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.3939-3944
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• 2014

Background: To elucidate the role of rapamycin and PF4 on apoptosis regulation via Bax (pro-apoptosis), Bcl-2 (anti-apoptosis) and survivin activation on the growth in the 1-methyl-1-nitrosourea-induced invasive breast carcinoma model. Materials and Methods: Thirty five female Sprague Dawley rats at age 21-day old were divided into 4 groups; Group 1 (control, n=10), Group 2 (PF4, n=5), Group 3 (rapamycin, n=10) and Group 4 (rapamycin+PF4, n=10). MNU was administered intraperitionally, dosed at 70mg/kg body weight. The rats were treated when the tumors reached the size of $14.5{\pm}0.5mm$ and subsequently sacrificed after 5 days. Rapamycin and PF4 were administered as focal intralesional injections at the dose of $20{\mu}g$/lesion. The tumor tissue was then subjected to histopathological examinations for morphological appraisal and immunohistochemical assessment of the pro-apoptotic marker, Bax and anti-apoptotic markers, Bcl-2 and survivin. Results: The histopathological pattern of the untreated control cohort showed that the severity of the malignancy augments with mammary tumor growth. Tumors developing in untreated groups were more aggressive whilst those in treated groups demonstrated a transformation to a less aggressive subtype. Combined treatment resulted in a significant reduction of tumor size without phenotypic changes. Bax, the pro-apoptotic marker, was significantly expressed at higher levels in the rapamycin-treated and rapamycin+PF4-treated groups compared to controls (p<0.05). Consequently, survivin was also significantly downregulated in the rapamycin-treated and rapamycin+PF4-treated group and this was significantly different when compared to controls (p). Conclusions: In our rat model, it could be clearly shown that rapamycin specifically affects Bax and survivin signaling pathways in activation of apoptosis. We conclude that rapamycin plays a critical role in the induction of apoptosis in MNU-induced mammary carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5753-5757
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• 2012

Apoptosis, also known as cell suicide or programmed cell death, removes unwanted and genetically damaged cells from the body. Evasion of apoptosis is one of the major characteristic features of rapidly proliferating tumor cells. Chemopreventive agents inhibit or suppress tumor formation through apoptotic induction in target tissues. The aim of the present study was to investigate the pro-apoptotic potential of lupeol during 7,12-dimethylbenz(a) anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Topical application of 0.5% DMBA three times a week for 14 weeks in the buccal pouches of golden Syrian hamsters resulted in oral squamous cell carcinoma. The expression pattern of apoptotic markers was analyzed using immunohistochemistry (p53, Bcl-2, Bax) and ELISA reader (caspase 3 and 9). In the present study, 100% tumor formation with defects in apoptotic markerexpression pattern was noticed in hamsters treated with DMBA alone. Oral administration of lupeol at a dose of 50mg/kg bw completely prevented the formation oral tumors as well as decreased the expression p53 and Bcl-2, while increasing the expression of Bax and the activities of caspase 3 and 9. The present study thus indicated that lupeol might inhibit DMBA-induced oral tumor formation through its pro-apoptotic potential in golden Syrian hamsters.

• 대한화학회지
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• 제66권4호
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• pp.298-304
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• 2022

The present study was designed to investigate the molecular mechanisms of DK-5-62, a novel (-)-catechin derivative on HCT116 human colorectal cancer cells. DK-5-62 inhibited the proliferation in dose- and time-dependent manner accompanied by the morphological changes. Effects of DK-5-62 appeared to be mediated by the induction of apoptosis, as manifested through DNA-binding dye Hoechst 33258 staining. Analysis of the mechanism of these events indicated that DK-5-62-treated cells exhibited an increased ratio of Bax/Bcl-2, resulting in the activation of caspase-9, caspase-3, and poly-ADP-ribose polymerase in a dose-dependent manner. Moreover, DK-5-62-induced apoptosis was accompanied by phosphorylation of the mitogen-activated protein kinase family, c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase. These results suggest that HCT116 cells are moderately sensitive to growth inhibition by DK-5-62 via apoptosis, as evidenced by activation of ERK/p38/Bcl-2 family signaling, as well as alteration in caspase-9 and caspase-3.

• 대한소아치과학회지
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• 제33권1호
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• pp.13-24
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• 2006

신경세포자멸사는 저산소 및 허혈환경에서 일어나며 이러한 세포죽음은 reactive oxident species (ROS) 생성을 동반함이 알려져있다. 그러나, 저산소 및 허혈환경에서 일어나는 세포자멸사의 기전 및 그 치료방법은 아직 정립되어 있지 않다. $CoCl_2$는 ROS를 생성하는 등 저산소환경과 유사한 조건을 초래하는 것으로 알려져 있다. Epigallocatechin gallate (EGCG)는 녹차의 polyphenol성분으로서 세포성장과 죽음에 다양한 약리학적 효과를 나타냄이 알려져 있다. 본 연구는 PC12세포에서 $CoCl_2$에 의한 세포자멸사기전을 밝히고 이에 미치는 EGCG의 효과를 조사하는데 목적이 있다. Cell viability는 MTT 측정으로 조사되었고, DNA fragmentation은 DNA laddering으로 조사되었다 Bcl-2와 Bax발현 정도는 RT-PCR로, caspase-3와 -9의 활성은 spectrophotometer, caspase-8의 활성은 flow cytometry에 의해 측정되었다. 미토콘드리아에서 세포질로 분비된 cytochrome c는 western blot으로, -분해된 DNA양과 미토콘드리아 세포막전위 $({\Delta}{\psi}_m)$는 FACScan으로 조사되었다. $CoCl_2$ 투여로 PC12 세포수는 용량 및 시간 의존형태로 감소하였고, genomic DNA fragmentation이 발생하였다. $CoCl_2$ 투여로 야기된 cell viability의 감소와 DNA fragmentation은 EGCG 전처치에 의해 억제되었다. $CoCl_2$는 세포용적팽창과 condensed nuclei 같은 형태적 변화를 일으켰으며, apoptotic peak, ${\Delta}{\psi}_m$ 감소 및 cytochrome c 유리를 야기하였다. EGCG는 $CoCl_2$에 의한 세포형태변화, apoptotic peak, ${\Delta}{\psi}_m$ 소실 및 cytochrome c유리를 억제시켰다. $CoCl_2$는 Bcl-2 발현을 감소시켰지만, Bax 발현에는 영향을 미치지 않았다. EGCG는 $CoCl_2$에 의해 야기된 Bcl-2 발현 감소를 억제시켰다. $CoCl_2$는 caspase-3, -8, 그리고 -9의 활성을 증가시켰으며, EGCG는 그 정도를 감약시켰다. ROS 제거제인 NAC (N-acetyl-cysteine)은 EGCG의 결과와 같은 양상으로 $CoCl_2$에 의 한 세포자멸사를 억제시켰다. 본 실험결과는 PC12 세포에서 $CoCl_2$가 미토콘드리아 의존 및 death receptor 의존 기전으로 세포자멸사를 일으키며, EGCG는 세포자멸사기 전을 억제시킴으로 신경보호기능을 가짐을 시사하였다.

• Clinical and Experimental Pediatrics
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• 제52권6호
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• pp.696-700
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• 2009

목 적 : Artemisinin은 인체에 대한 부작용이 적고 항말라리아 효능 뿐 아니라 강력한 항암효과가 있음이 알려져 있다. 저자들은 오까야마 약학대학에서 합성 된 350여개의 endoperoxide ring구조를 가진 artemisinin 유도체를 선별검사 하여 HL-60세포 주에 강력한 세포독성을 보여 준 c-127의 세포고사 유도 여부와 그 분자유전학적 기전을 알아보고자 하였다. 방 법 : HL-60세포는 RPMI 1640배지로 배양하였고 세포 생존율은 MTT분석으로 측정하였다. 세포고사 여부는 DNA추출과 전기영동법으로 확인하였으며 세포고사 유도 기전은 western blotting을 시행하여 알아보았다. 결 과 : C-127이 세포고사를 유도하여 HL-60세포의 세포 생존력을 농도 의존적으로 감소시켰다. C-127의 이런 항암효과의 분자 유전학적 기전으로는 caspase-8,3 활성화, Bcl-2 family인 Bid분절, JNK 인산화와 c-Jun 발현이 관여하였다. 결 론 : C-127이 HL-60 세포에서 세포고사를 유도하여 강력한 항암효과를 발현하였고, 그 기전으로 caspase cascade, Bcl-2 family, JNK인산화와 c-Jun활성화가 관여하였다.

• 한국진공학회:학술대회논문집
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• 한국진공학회 2001년도 창립10주년 제20회 학술발표회
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• pp.127-127
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• 2001

• Molecules and Cells
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• 제19권2호
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• pp.185-190
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• 2005

The chicken oviduct is a dynamic organ that produces secretory proteins such as ovalbumin and its cells undergo cell proliferation and differentiation. There has been no study of the cellular mechanism involved in cell death in the chicken oviduct. Therefore, this study has focused on the study of apoptosis in primary oviduct cells. Because ceramide is known to activate apoptosis in tumor cells and is produced in the oviduct, we used an exogenous ceramide analog to induce cell death. The viability of ceramide-treated chicken oviduct cells decreased in a dose-dependent manner and apoptotic cells were detected by staining with annexin V. The expression of apoptosis-related genes was assessed by RT-PCR and bcl-2 mRNA was found to decrease after exposure to ceramide while Bcl-x mRNA increased 12 h post-treatment. In addition, caspase-3 was expressed strongly in the early stages of apoptosis, while caspase-1 and -9 transcripts increased at later times. We conclude that ceramide induces apoptosis in oviduct-derived primary cells via a caspase- and bcl-2-dependent pathway.

• 한국전기전자재료학회:학술대회논문집
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• 한국전기전자재료학회 2009년도 추계학술대회 논문집
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• pp.48-48
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• 2009

최근 빠른 동작속도와 고 집적도를 얻기 위해 metal oxide semiconductor field effect transistor (MOSFET) 의 크기는 계속 해서 줄어들고 있다. 동시에 게이트의 절연층도 얇아지게 된다. 절연층으로 사용되는 $SiO_2$ 의 두께가 2nm 이하로 얇아 지게 되면 터널링에 의해 누설 전류가 발생하게 된다. 이 문제를 해결하기 위해 $SiO_2$ 를 대체할 고유전체 물질의 연구가 활발하다. 고유전체 물질 중에는 $ZrO_2,\;Al_2O_3,\;HfO_2$ 등이 많이 연구 되어 왔다. 하지만 유전상수 이외에 band gap energy, thermodynamic stability, recrystallization temperature 등의 특성이 좋지 않아 대체 물질로 문제점이 있다. 이를 보안하기 위해 산화물을 합금과 결합시키면 서로의 장점들이 합쳐져 기준들을 만족하는 물질을 만들 수 있고 $HfAlO_3$가 그 중 하나이다. Al를 첨가하는 이유는 문턱전압을 낮추기 위해서다. $HfAlO_3$는 유전상수 18.2, band gap energy 6.5 eV, recrystallization temperature 800 $^{\circ}C$이고 열역학적 특성이 안정적이다. 게이트 절연층은 전극과 기판사이에 적층구조를 이루고 있어 이방성인 드라이 에칭이 필요하고 공정 중 마스크물질과의 선택비가 높아야한다. 본 연구는 $HfAlO_3$박막을 $BCl_3/Ar,\;N_2/BCl_3/Ar$ 유도결합 플라즈마를 이용해 식각했다. 베이스 조건은 RF Power 500 W, DC-bias -100 V, 공정압력 15 mTorr, 기판온도 40 $^{\circ}C$ 이다. 가스비율, RF Power, DC-bias, 공정 압력에 의한 마스크물질과 의 선택비를 알아보았다.

• Archives of Pharmacal Research
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• 제24권4호
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• pp.349-354
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• 2001

Curcumin, a dietary pigment in turmeric, posseses anti-carcinogenic and anti-metastatic properties. The present study was conducted to study in vitro chemopreventive effects of curcumin in transformed breast cells. Here, we show that curcumin inhibits H-ras-induced invasive phenotype in MCF10A human breast epithelial cells (H-ras MCF10A) and downregulates matrix metalloproteinase (MMP)-2 dose-dependently. Curcumin exerted cytotoxic effect on H-ras MCF10A cells in a concentration-dependent manner. Curcumin-induced cell death was mainly due to apoptosis in which a prominent downregulation of Bcl-2 and upregulation of Bax were involved. We also suggest a possible involvement of caspase-3 in curcumin-induced apoptosis. Curcumin treatment resulted in the production of reactive oxygen species (ROS) in H-ras MCF10A cells. Apoptotic event by curcumin was significantly inhibited by pretreatment of an antioxidant N-acetyl-$_L$-cysteine (NAC), suggesting redox signaling as a mechanism responsible for curcumin-induced apoptosis in H-ras MCF10A cells. Taken together, our results demonstrate that curcumin inhibits invasion and induces apoptosis, proving the chemopreventive potential of curcumin .