• 약학회지
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• 제53권1호
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• pp.6-11
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• 2009

This study investigated the antiproliferative effect of the EtOH extract from Litsea japonica. The extract markedly inhibited the growth of HL-60 cells. When treated with the extract, several apoptosis events like as DNA fragmentation, chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. The extract decreased the Bcl-2 expression, whereas the Bax expression was increased. Caspase-9 and -3 were activated and poly (ADP-ribose) polymerase was cleaved. The results suggest that the antiproliferative effect of L. japonica in HL-60 appears to arise from apoptosis induction via the down-regulation of Bcl-2 and the activation of caspases.

• 대한본초학회지
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• 제21권4호
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• pp.51-58
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• 2006

Objectives : In this study, we investigate that Ulmi cortex extract contributes to growth inhibitory effect and anti-cancer activity on the HT-29 human colon cancer cells. Methods : Ulmi cortex was extracted from the leaves of the plant using water. The Ulmi cortex extract was treated to different concentrations for 24 hr. Growth inhibitory effect was analyzed by measuring FACS study and MTT assay. Cell cycle inhibition was confirmed by kinases assay. Cell apoptosis was confirmed by surveying caspases cascades activation using Western blot. Results : Exposure to Ulmi cortex extract (0.4mg/ml) results in an inhibitory effect on cell growth in HT-29 cells. Growth inhibition by Ulmi cortex extract in HT-29 cells was related with the inhibition of proliferation and induction of apoptosis. The Ulmi cortex extract induces G1-cell cycle arrest and DNA fragmentation in HT-29 cells. Furthermore, Ulmi cortex extract induces cell apoptosis through the activation of caspases-3 and PARP cleavage. Conclusion : Ulmi cortex extract induces apoptosis in human colon cancer cells, therefore, we suggest that Ulmi cortex extract can be used as a novel class of anti-cancer drugs.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7291-7296
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• 2014

Different plant parts of Flacourtia indica have long been used in Ayurvedic medicine. Previous studies have demonstrated that the methanolic extract of F. indica possess anti-inflammatory properties. The present study was aimed at investigating the anticancer effects of methanol extract of Flacourtia indica (FIM) aerial parts in human colon cancer (HCT116) cells. Treatment of cells with FIM at a concentration of $500{\mu}g/ml$ for 24 hours significantly reduced cell viability and induced apoptosis, which was associated with the increased cytoplasmic expression of cytochrome c, activation of caspase-3, and the cleavage of poly-(ADP-ribose) polymerase. Incubation with FIM also inhibited the levels of Bcl-2, Bcl-xl and survivin, which are the markers of cell proliferation, whereas the expression of Bax remained unchanged. Treatment with FIM led to the generation of reactive oxygen species (ROS) in a concentration-dependent manner. Pharmacological inhibition of ROS generation by pretreatment of cells with N-acetyl cysteine abrogated FIM-induced apoptosis in HCT116 cells. Thus, these results demonstrate that FIM has anti-proliferative and pro-apoptotic effects in HCT116 cells and the effects are, at least in part, due to the ROS dependent activation of caspases.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5983-5987
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• 2013

Radix Tetrastigma Hemsleyani Flavone (RTHF) is widely used as a traditional herb for its detoxification and anti-inflammation activity. Recently, several studies have shown that RTHF can inhibit growth and induce apoptosis in human cancer cell lines. However, the mechanisms are not completely understood yet. In this study we investigated the potential effects of RTHF on growth and apoptosis in human lung adenocarcinoma A549 cells as well as its mechanisms. A549 cells were treated with RTHF at various concentrations for different times. In vitro the MTT assay showed that RTHF had obvious anti-proliferation effects on A549 cells in a dose- and time-dependent manner. Cell morphological changes observed by inverted microscope and Hoechst33258 methods were compared with apoptotic changes observed by fluorescence microscope. Cell apoptosis inspected by flow cytometry showed significant increase in the treatment group over the control group (P<0.01). Expression of apoptosis related Bax/Bcl-2, caspases and MAPK pathway proteins were detected by Western blotting. The results showed that RTHF up-regulated the Bax/Bcl-2 ratio and cle-caspase3/9, cle-PARP expression in a dose-dependent manner. Expression of p-p38 increased, p-ERK decreased significantly and that of p-JNK was little changed in the RTHF group when compared with the control group. These results suggest that RTHF might exert anti-growth and apoptosis activity against lung cancer A549 cells through activation of caspases and Bcl-2 family proteins and the MAPK pathway, therefore presenting as a promising therapeutic agent for the treatment of lung cancer.

• BMB Reports
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• 제42권8호
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• pp.511-515
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• 2009

Downstream of Bid (DOBI) known as Pus10, has been identified as a modulator of TRAIL-induced cell death using RNAi library screening. The crystal structure of DOBI has revealed that it is a crescent-shaped protein containing the pseudouridine synthase catalytic domain and a THUMP-containing domain. Here, we demonstrated that DOBI is expressed in various tissues such as heart and lung, and is also expressed in various tumor cells such as HeLa and A549. Although ectopic expression of DOBI does not promote TRAIL death signaling in HeLa cells, knock-down of DOBI expression using shRNA inhibited TRAIL death signaling. DOBI is cleaved into a 54 kD cleaved DOBI during cell death, and the recombinant DOBI protein can be directly cleaved by caspases-3, or -8 in vitro. Together, these data suggest that the cleaved DOBI may acquire a new function, possibly by cooperating with tBid in the mitochondrial event of cell death caused by TRAIL.

• 한국식품영양과학회지
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• 제42권9호
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• pp.1363-1369
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• 2013

본 연구에서는 플라보노이드 계열 중의 하나인 luteolin을 이용하여 TRAIL에 저항성을 가지는 T24 방광암세포에서 TRAIL 저항성 극복 가능성을 조사하였다. 본 연구의 결과에 의하면 luteolin 및 TRAIL 각각 단독 처리 시 세포증식에 전혀 영향을 미치지 못한 농도의 복합 처리 시 세포증식억제 효과가 크게 증가하였음 알 수 있었다. 이러한 증식억제와 연관된 aspoptosis 유도는 caspase-8의 활성화에 의한 tBid의 발현 증가와 pro-apoptotic 인자인 Bax의 발현 증가로 인한 caspase-9 및 -3의 활성화로 이어지는 type II apoptosis에 의한 것이라 추측되며, 이러한 가정은 각각의 caspase 선택적 저해제를 이용하여 재확인 하였다. 본 연구결과는 TRAIL에 저항성을 보이는 암세포에 luteolin이 감수성을 높이는데 효과적일 수 있으며, 암세포에 대한 combination therapy를 위한 기초자료로 활용성이 높을 것으로 사료된다.

• 대한치과교정학회지
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• 제33권6호
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• pp.453-463
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• 2003

본 연구는 MC3T3El 조골세포가 저산소증에 반응하여 유발될 수 있는 세포 고사조절 기전을 구명하고자 함에 목적이 있다. $2\%$ 저산소증의 조건하에서 MC3T3El 조골세포는 DNA 사다리 분절 헝성을 보였으며 형광성 염료인 Hoechst 33258로 염색된 핵 구조 형태 관찰시 시간이 지남에 따라 세포고사 현상을 관찰할 수 있었다 Pancaspase 억제제인 Z-VAD-FMK나 특정한 caspase-3 억제제인 Z-DEVD-CHO로 사전 처치하였을 경우에는 저산소증에 의한 DNA 사다리 분절형성이 농축에 비례하여 억제되었다. caspase-3류의 프로테아제(DEVDase) 활성 증가가 세포고사 중에 관찰되었으나 caspase-1 (YVADase)의 활성은 없었다. 어떤 caspase가 세포고사에 관여하는지를 확인하기 위하여 anti-caspase-3 또는 anti-caspase-6의 항체를 이용한 western blotting이 시행되었다. caspase-3의 활성산물에 해당하는 17-KDa단백질과 caspase-6의 활성산물인 20-KDa 단백질이 세포용해물에서 발생되었다. 또한 시간 경과와 더불어 caspase-6의 활동의 상징인 Lamin A의 분열을 일으켰으며, 사이토크롬 C를 cytosol로 방출하였다. 이로써 저산소증에 의한 조골세포의 고사 과정에 사이토크롬 C의 방출이 포함된 caspase의 활성이 관여한다는 것을 확인할 수 있었다.

• BMB Reports
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• 제42권2호
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• pp.96-100
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• 2009

Aromatic (ar)-turmerone from turmeric oil displays anti-tumorigenesis activity that includes inhibited cell proliferation. This study investigated ar-turmerone-mediated apoptotic protein activation in human lymphoma U937 cells. Ar-turmerone treatment inhibited U937 cell viability in a concentration-dependent fashion, with inhibition exceeding 84%. Moreover, the treatment produced nucleosomal DNA fragmentation and the percentage of sub-diploid cells increased in a concentration-dependent manner; both are hallmarks of apoptosis. The apoptotic effect of ar-turmerone was associated with the induction of Bax and p53 proteins, rather than Bcl-2 and p21. Activation of mitochondrial cytochrome c and caspase-3 demonstrated that the activation of caspases accompanied the apoptotic effect of ar-turmerone, which mediated cell death. These results suggest that the apoptotic effect of ar-turmerone on U937 cells may involve caspase-3 activation through the induction of Bax and p53, rather than Bcl-2 and p21.

• Journal of Microbiology and Biotechnology
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• 제19권3호
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• pp.286-290
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• 2009

In the course of screening for substances inhibiting apoptosis of U937 human leukemia cells induced by etoposide ($10\;{\mu}g/ml$), Forsythiae fructus, which showed a high level of inhibition, was selected. The regulating compounds were purified from the ethyl acetate extract by silica gel column chromatography and HPLC. The active substance was purified and identified as rengyolone by spectroscopic methods. This compound showed inhibitory activity on caspase-3 induction, a major protease of the apoptosis cascade, with an $IC_{50}$ value of $38.96\;{\mu}M$ after 8 h of etoposide treatment in U937 cells. The expression level of caspase-3 and poly(ADP-ribose) polymerase (PARP) were dose-dependently inhibited by the compound, suggesting that rengyolone inhibits etoposide-induced apoptosis via downregulation of caspases.

• 생명과학회지
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• 제27권2호
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• pp.164-171
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• 2017

본 연구에서는 인간 자궁경부암세포주에서 S-allylcysteine (SAC)이 세포자멸경로에 중요한 역할을 담당하는 initiator caspase의 하나인 caspase-9와 effector caspase에 속하는 caspase-3 및 caspase-7 그리고 DNA 복구에 관여하는 poly ADP-ribose polymerase (PARP)의 발현조절에 미치는 영향과, SAC에 의한 이러한 세포자멸 및 DNA 복구 관련 단백질의 발현변화가 세포증식억제를 통한 기능적 작용을 유발하는지를 조사하였다. 단백질 발현분석 결과, 특히 50 mM의 SAC로 48시간 동안 처리하였을 경우, procaspase-3, -7, -9 및 PARP의 발현은 각각 94%, 38%, 95% 및 64% 감소되었으며, 이와 반대로 caspase-3, -7, -9 및 cleaved-PARP의 발현은 현저히 증가되었다. 또한 cell proliferation assay 결과, 20 mM 이상의 SAC 처리는 6, 12, 24 및 48시간에서 농도 및 시간 의존적인 세포증식 억제효과를 나타내었다. 이러한 결과는 SAC 처리가 자궁경부암세포의 증식을 억제하며, 이에 대한 가능한 분자적 작용기전들 중의 하나로 세포자멸과정 중 initiator caspase의 하나인 caspase-9의 활성을 유도하고 이에 따른 effector caspase인 caspase-3과 caspase-7의 활성을 촉진시킬 뿐만 아니라 DNA 복구에 관여하는 PARP의 불활성화를 초래함으로써 세포자멸 유도에 관여하는 것으로 사료된다.