• 동의생리병리학회지
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• 제26권3호
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• pp.287-292
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• 2012

The results of this study intended to clarify the apoptotic effects of curcumin on Epstein-Barr virus transformed human B lymphoma (EBV-B) cells are summarized as follows: It was found that curcumin induced endoplasmic reticulum(ER) stress as well as apoptotic cell death in EBV-B cells, although the magnitude of action was insignificant. When EBV-B cells activated by pokeweed mitogen (PWM) were treated with the same concentrations of curcumin, it was found that higher ER stress (GRP78, P-PERK, XBP-1, ATF6, and CHOP expressed) increased unfold protein response (UPR) and thus, apoptosis attributed to ER stress, compared to non-activated EBV-B cells In conclusion, it is expected that curcumin will play an important role for leukemia treatment.

• 동의생리병리학회지
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• 제21권6호
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• pp.1513-1519
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• 2007

Yukwool-tang (YWT) is a traditional Chinese medicine, which has been used for patients suffering from a uterine disease in Oriental medicine. In the present study, it was examined the biochemical mechanisms of apoptosis by YWT in human cervical carcinoma HeLa cells. It was found that YWT could inhibit the cell growth of HeLa cells in a dose-dependent manner, which was associated with apoptotic cell death such as formation of apoptotic bodies and DNA fragmentation. Flow cytometry analysis confirmed that YWT treatment increased populations of apoptotic-sub-G1 phase of the cell cycle. We observed the p53-independent induction of p21 proteins, down-regulation of anti apoptotic Bcl-2 expression and proteolytic activation of caspase-3 in YWT-treated HeLa cells. YWT treatment also concomitant degradation and/or inhibition of poly (ADP-ribose) polymerase (PARP), phospholipase C-1 ($PLC{\gamma}1$), ${\beta}-catenin$ and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Taken together, these findings partially provide novel insights into the possible molecular mechanism of the anti-cancer activity of YWT.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3395-3403
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• 2016

Conjugated linoleic acid, a functional lipid, produced from Lactobacillus plantarum (LP-CLA), has been demonstrated to possess apoptotic activity. The anti-proliferative and apoptotic potential of LP-CLA was here evaluated in vitro using the MDA-MB-231 human breast cancer cell line as a model system. Proliferation of MDA-MB-231 cells was inhibited with increasing concentrations of LP-CLA with altered morphological features like cell detachment, rounding of cells and oligonucleosomal fragmentation of DNA. Flow cytometry confirmed the apoptotic potential of LP-CLA by ANNEXIN V/PI double staining. Furthermore, outcome results indicated that the apoptosis was mediated by downregulation of the NF-${\kappa}B$ pathway which in turn acted through proteasome degradation of $I{\kappa}B{\alpha}$, inhibition of p65 nuclear translocation, release of cytochrome-C from mitochondria and finally overexpression of Bax protein. Thus, conjugated linoleic acid, a natural product derived from probiotics, could therefore be a possible potential chemotherapeutic agent due to its apoptotic activity against estrogen receptor negative breast cancer cells.

• The Korean Journal of Physiology and Pharmacology
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• 제21권6호
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• pp.599-607
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• 2017

Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and presumed to support their increased growth and proliferation. This study examined the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its mechanism for cell death in Saos2 human osteosarcoma cells. FOB human osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2 cells was especially weak. JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, potently inhibited L-leucine uptake in Saos2 cells. As expected, the intrinsic ability of JPH203 to inhibit L-leucine uptake was far more efficient than that of BCH in Saos2 cells. Likewise, JPH203 and BCH inhibited Saos2 cell growth with JPH203 being superior to BCH in this regard. Furthermore, JPH203 increased apoptosis rates and formed DNA ladder in Saos2 cells. Moreover, JPH203 activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. These results suggest that the inhibition of LAT1 activity via JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by inducing the intracellular depletion of neutral amino acids essential for cell growth in Saos2 human osteosarcoma cells.

• 대한한의학회지
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• 제23권3호
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• pp.200-210
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• 2002

Objectives: Dojeckjiyu-tang has been used to treat Hwaseol & Jeokri. The object of this study is examination of the treatment effect of Dojeckjiyu-tang for ulcerative colitis of the mouse descending colon. Methods and Materials : Twenty-one rats were divided into 3 groups and treated as follows: the control group was untreated mice. The UCE group was ulcerative colitis elicited mice. The DJT group was Dojeckjiyu-tang treated mice after ulcerative colitis elicitation. The groups were examined with common morphology, paneth cells in intestinal crypt, absorptive cells and goblet cells in epithelium, cell division in mucose, COX-1 as mucosal protector, COX-2 (which appears to play an important role in inflammation), IL-2R-, ICMA-1-inducing cellular immuno-chainreaction, and the distribution of apoptotic cells. Results: 1. The morphology of colonic mucosa from UCE mice: the disappearance of epithelium and intestinal propria in hemorrhagic erosions were seen, but in the morphology of colonic mucosa from DJT-treated mice, the configuration of epithelium and intestinal propria were the same as normal. 2. The distribution of goblet cells and absorptive cells with microvilli in intestinal propria from UCE mice: a noticeable decrease of goblet cells and absorptive cells with microvilli were seen, but with the distribution of goblet cells and absorptive cells with microvilli in intestinal propria from DJT -treated mice, the configuration of goblet cells and absorptive cells with microvilli were the same as normal. 3. The immunohistochemical stain for BrdD in colonic mucosa and COX-1 in lamina propria from UCE mice: BrdU positive cells and COX-1 positive cells in the region of hemorrhagic erosion disappeared, but in the immunohistochemical stain for BrdU in colonic mucosa and COX-1 in lamina propria from DIT-treated mice, BrdU positive cells and COX-1 positive cells were seen. 4. The immunohistochemical stain for COX-2 in lamina propria, IL-2R-in lamina propria, intestinal propria and submucosa and ICMA-1 in intestinal propria and submucosa from DCE mice: a noticeable increase COX-2, IL-2R-, ICMA-1 positive cells were seen, but in the immunohistochemical stain for COX-2 in lamina propria, IL-2R-in lamina propria, intestinal propria and submucosa and ICMA-1 in intestinal propria and submucosa from DJT-treated mice, a numerical decrease of COX-2, IL-2R-, ICMA-1 positive cells was observed. 5. The distribution of apoptotic cells in epithelium and lamina propria from UCE mice: a noticeable increase of apoptotic cells in region of hemorrhagic erosion was seen, but in the distribution of apoptotic cells in epithelium and lamina propria from DJT-treated mice, a remarkable decrease of apoptotic cells was seen. Conclusions: According to the above results, Dojeckjiyu-tang has a moderate effect on ulcerative colitis in descending colon.

• 사상체질의학회지
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• 제14권1호
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• pp.100-111
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• 2002

1. The Purpose of study An experimental study has done to examine the effect of defense on gastric mucosal damage of Jowesungcheong-tang. 2. The Material and Method of study Mice had intragastric injected with JST extract before indome thacin treatment which induces hemorrh age erosion artificially. General morphology, infiltrative cell in mucosa, the distribution of UEA-I, COX-1, MAC-1. ICAM, and Apoptotic cell were objected (Ahhreviation) JST :Jowesungcheong-tang, UEA-I : ulex europaeus agglutinin-I, COX-1: cyclooxyhenase-1, ICAM : intercellular adhesion molecule-1, GPE : Gastropathy elicitated mice 3. The results and Conclusions of study 1) The degree of hemorrhage erosion in GPE-group had increased conspicuously in gastric gland proper. JST -group were the same as normal 2) The noticeable increase of granular lecocytes and lymphocytes in GEP-group were seen, but in JST group, the configuration is decreased 3) The decrease of UEA-I positive reacted cells, COX-1, surface epithelial cells and the increase of MAC-l positive cells, ICAM-l positive cells had shown in GPE-group, but in JST-group UEA-I positive cells, COX-1 surface epithelial cells were in creased and MAC-1 positive cells, ICAM-l positive cells were decreased than GPE-group. 4) A number of apoptotic cells were distributed in hemorrhage erosion. The remarkable decrease of apoptotic cells were shown in JST-group.

• 대한치과교정학회지
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• 제31권1호
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• pp.71-83
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• 2001

악안면 부위에서 가장 빈번히 발생하는 선천적 기형의 하나인 구개열은 그 원인요소가 명확히 밝혀져 있지는 않지만 구개발생 과정 중 어느 한 단계에서의 이상으로 발생하며 양측 구개판의 융합 후 융합상피의 제거가 이루어지지 않는 것도 그 원인의 하나로 알려져 있다. 본 연구는 구개발생시 구개판 융합상피의 제거가 아포프토시스에 의한 것임을 확인하고 아포프토시스가 일어나는 시기와 위치를 규명하기 위해 시행되었다. 체중 200gm내외의 암컷흰쥐 12마리를 체중 250gm내외의 수컷흰쥐와 교배시켜 16.0일, 16.5일, 16.75일, 17.0일 태아를 얻었으며 각 태아에서 두부만을 파라핀 포매하여 전두절단 하였다. 조직절편에서 형태학적 소견을 관찰하기 위한 H-E 염색과 아포프토시스를 인지하기 위한 TdT염색을 시행한 후 광학현미경을 통해 관찰하여 다음과 같은 결론을 얻었다. 1. 16.0일과 16.5일 된 태아의 표본에서 접촉전의 양측 구개판의 내측단 상피에서는 아포프토시스를 관찰할 수 없었으며, 구개판의 접촉 직후 상피세포간의 융합이 이루어지는 부위에서는 극히 소수의 아포프토시스 세포들만이 관찰되었다. 2. 16.75일 된 태아의 표본에서 연속성을 거의 잃지 않은 정중 상피융합에서는 아포프토시스를 거의 관찰할 수 없었으나, 비강측과 구강측의 상피삼각 그리고 비중격과 구개판이 접촉하는 부위, 특히 비중격의 외측연과 접촉하는 부위에서는 다수의 아포프토시스 세포들이 관찰되었다. 3. 16.75일 된 태아의 표본에서 정중 상피융합이 연속성을 잃고 상피섬들로 나뉘어지는 시기 에서는 상피섬과 상피삼각부위에서 증가된 아포프토시스 세포들을 관찰할 수 있었으며 근접한 구강, 비강상피에서도 다수의 아포프토시스세포들이 관찰되었다. 4. 17.0일 된 태아의 표본에서 상피섬이 많이 소실되어 간엽조직에 의한 융합이 이루어지고 있는 부위에서는 아포프토시스 세포들이 거의 관찰되지 않았으나 상피삼각부위와 구강, 비강상피에서는 아직도 다수의 아포프토시스 세포들이 관찰되었다. 이상의 결과로 흰쥐 태아의 구개발생시 구개융합부위의 상피세포가 아포프토시스에 의해 제거된다는 사실을 알 수 있었으며 이러한 아포프토시스에 의한 융합상피세포의 제거는 주로 구개융합의 후반기에 상피섬과 상피삼각 부위에서 일어난다는 사실을 알 수 있었다.

• 대한수의학회지
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• 제40권2호
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• pp.213-220
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• 2000

Experimental induction of apoptosis by bacterial lipopolysacchardie is useful for understanding the role of apoptosis cell death in clinical endotoxin shock or septic shock. Thirty three mice were injected intraperitoneally with D-galactosamine (20mg) and lipopolysac-charide ($5{\mu}g$) per mouse. Five to eight mice per each experimental group were sacrificed at 6, 12, 24, 48 and 72 hrs post administration. The cells with apoptotic bodies in H-E stained sections were investigated histologically. Development of the apoptotic bodies in livers was observed in 11 of 33 mice (33.3%). These cells were diffusely or collectively appeared only in liver but not observed in kidney, thymus and spleen. Mean percentage of the cells with apoptotic bodies in the livers were 0.32, 4.34 and 5.50% respectively at 6, 12, and 24 hrs post administration. But percentage of these apoptotic cells were fairly less in 48 and 72 hrs post administration. The percentages of cells with 3 to 9 apoptotic bodies per cell were 70~90% of all apoptotic cells. The cells with more apoptotic bodies than limit number at 12 to 72 hrs post administration were belived to be necrosed. The percentage of positive cells by TUTNEL methods were 0.00~0.08, 0.00~052, 1.63~4.18, 12.41~20.21 respectively at control, 6, 12 and 24 and less than 0.01% at 48 and 72 hrs. The above results suggest that development of liver cell apoptosis by lipopolysaccharide ($5{\mu}g$) and D-glatosamine (20mg) was less at 6 hrs and markedly increased at 12 to 24 hrs and then was fairly less at 48 and 72 hrs post administration.

• Applied Microscopy
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• 제40권2호
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• pp.81-88
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• 2010

변태중인 참개구리(Rana nigromaculata) 유생의 상피에서 세포자멸사가 초래된 세포를 확인하고 이들의 핵과 세포질에서 나타나는 퇴행과정의 미세구조 변화를 TUNEL 염색법과 투과전자현미경 관찰을 통해 분석하였다. 꼬리의 퇴화가 진행되는 Shumway 발생단계 31기부터 33기까지의 유생 상피는 다층의 입방형세포로 이루어져 있었고, TUNEL 염색으로 관찰한 결과, 상피 전역에 걸쳐 광범위한 세포자멸사가 진행되고 있음을 확인할 수 있었다. 자멸사에 의해 초래되는 상피세포의 초기 변형은 먼저 핵에서 관찰되었는데, 염색질이 응축되어 핵막 주변부로 편재되었고 핵의 분절과 세포질의 응축, 그리고 세포막의 변형이 뒤따르는 것으로 확인되었다. 이어서 세포질의 분절에 의해 자멸소체가 형성되었는데 막으로 둘러싸인 소체 내부에서는 비교적 잘 보존된 형태의 세포소기관들이 관찰되었다. 자멸사가 초래된 세포들은 상피내 대식세포(intraepithelial macrophage)로 추정되는 인접 세포들에 의해 탐식되어 잔여소체를 형성하였으며, 급속한 퇴화과정을 거쳐 층판구조를 지닌 소포의 형태로 변형된 후 세포질에서 소멸됨이 확인되었다.

• 대한수의학회지
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• 제41권2호
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• pp.203-210
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• 2001

방사선 피폭선량의 예측을 위한 방사선 민감 지표 모델 개발을 위하여 코발트-60 감마선과 의료용 싸이크로트론 50 MeV($p{\to}RBe^+$) fast neutron을 0.25 Gy에서 1 Gy의 선량을 랫드에 각각 전신 조사한 후 말초혈액내 임파구와 소장에 음와세포의 형태학적 변화를 apoptotic fragment assay법을 이용하여 관찰하였다. 모든 방사선조사군에서 음와세포와 말초 임파구에 아포토시스의 유도가 증가된 것이 관찰되었으며, 이것은 방사선이 방사선 민감세포의 아포토시스 유도를 자극한 것으로 보인다. 상기의 결과는 아포토시스가 손상된 세포를 제거하므로 손상된 방사선 민감 표적 장기의 항상성 유지에 중요한 역할을 하는 것으로 판단되었다. Apoptotic fragments의 발생빈도에 대한 선량-반응곡선에 있어서 음와세포는 중선자 조사군이 $y=0.3+(6.512{\pm}0.279)D(r^2=0.975)$으로, 반면에 감마선 조사군은 $y=0.3+(4.435{\pm}0.473)D+(-1.300{\pm}0.551)D^2(r^2=0.988)$의 식을 얻었다. 그리고 말초 임파구에서는 감마조사군이 $y=3.5+(118.410{\pm}10.325)D+(-33.548{\pm}12.023)D^2(r^2=0.992)$의 식으로 나타났다. 이와 같이 감마선조사군은 공히 linear quadratic model 이였으나 중성자조사군은 linear model 로 관찰되었다. 조사된 세포의 종류와 상관없이 apoptotic fragments의 발생빈도와 조사 선량간의 유의한 효과가 있는 것으로 확인되었다. 이상의 결과에서 조사선량의 증가와 비례하여 방사선 민감 세포의 apoptotic fragments가 수적으로 증가하였으며, 고준위 방사선이 저준위 방사선보다 선량 반응 곡선과 시간 경과에 따른 영향이 보다 강한 것으로 인지되었으며, 음와세포의 apoptosis 유도에 대한 중성자선의 방사선 생물학적 효과비(RBE)는 1.919 였다. 그리고 모든 방사선조사군에서 방사선피폭 후 4시간과 6시간에 apoptosis 유도가 가장 많았으며, 음와세포의 형태학적 소견은 정상 대조군에서 관찰되지 않는 전형적인 apoptotic fragments가 나타났다. 따라서 음와 세포와 말초 임파구에서의 아포토시스 유도는 방사선 조사에 의한 세포 손상의 생물학적 영향 평가를 위한 검색 및 방사선 피폭선량 예측의 지표로 이용 가능할 것으로 사료됨.