• Advances in Traditional Medicine
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• 제3권3호
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• pp.151-156
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• 2003

The leaves of Mirabilis jalapa L contains protein fraction presumed ribosome-inactivating protein (RIP). RIP is a group of protein that has RNA N-glycosidase activity that is capable to inhibit protein synthesis. Protein fraction of the plant was shown to be cytotoxic on HeLa cell-line, however, the mechanism by which the protein kill the cells is not identified yet, whether trough apoptosis, necrosis, or other mechanism. This research aim to study the mechanism of cell death caused by the protein fraction isolated from the leaves of this plant on HeLa and Raji cell-line, as representative of different kind of cancer cells. Results showed that protein fraction isolated from the leaves of Mirabilis jalapa L was more cytotoxic to HeLa cell-line (LC50: 0.65 mg/ml) than to Raji cell-line (1.815 mg/ml) on 48 hours incubation time. Moreover, it was demonstrated that the death of HeLa cells caused by the protein fraction was due to induction of apoptosis, while on Raji cell-line was due to non-apoptosis way, presumably via necrosis.

• 동의생리병리학회지
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• 제23권6호
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• pp.1404-1408
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• 2009

Methanol extracts of Rubus Coreanus Miquel (RCM) were found to exhibit apoptosis induction of U937 human histiocytic leukemia cells. Treatment of RCM exerted strong cytotoxicity against U937 human leukemia cells. RCM induced apoptosis of U937 leukemia cells in a dose dependent manner. Nitric oxide (NO) production was increased in RCM-treated RAW264.7 macrophage cell line. RCM increased the p53 and $NF{\kappa}B$ gene and decreased the $I{\kappa}B$ gene expression in U937 cells. RCM also increased the $NF{\kappa}B$ protein expression, but decreased the PCNA and BcL-xL protein expression in cultured U937 cells. These data suggest that RCM are effective on the apoptosis induction of human leukemia cells and anti-cancer properties.

• 한국미생물·생명공학회지
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• 제47권1호
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• pp.43-53
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• 2019

The anticancer activity of guava (Psidium guajava L.) leaf extract (GLE) occurs via the induction of apoptosis in cancer cells. However, the mechanism behind GLE-induced apoptosis in the human hepatocellular carcinoma cell line HepG2 remains unclear. In the present study, we investigated the apoptotic effects and mechanism of action of GLE in cultured HepG2 cells. The results showed that GLE induced reactive oxygen species (ROS) synthesis and disrupted the mitochondrial membrane potential (${\Delta}{\Psi}m$). Moreover, GLE increased the expression of apoptotic pathway proteins, such as the cleaved forms of caspase-3, -8, and -9; the translocation of Bax and cytochrome c (cyt-c) from the mitochondria to the cytosol; and the downregulation of Bcl-2. In addition, p53 protein expression was increased upon GLE treatment. These observations indicate that the GLE-induced apoptosis in HepG2 cells is mediated by mitochondrial ROS generation, followed by caspase activation and cyt-c release, suggesting that GLE may be a promising candidate for the development of novel drugs for the treatment of liver cancers.

• 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.

• 한국식품영양과학회지
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• 제38권8호
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• pp.1008-1015
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• 2009

최근 다방면에서 효능이 알려지고 있는 로즈마리를 이용하여 apoptosis 유도기전을 해석하기 위하여 인간유래 자궁암 Hela 세포주를 대상으로 조사한 결과는 다음과 같다. 로즈마리 분획물 중 hexane층과 chloroform층의 처리 농도 의존적으로 Hela 자궁암세포의 저해활성은 현저하게 감소되었으며 이는 apoptosis 유도와 연관성이 있었다. 로즈마리 분획물 중 hexane층과 chloroform층의 처리에 의하여 apoptosis 억제에 관여하는 Bcl-2 단백질의 발현은 감소되었으며, apoptosis 유도에 관여하는 Bax 유전자의 발현은 농도 의존적으로 증가되었다. 로즈마리 분획물 중 hexane층과 chloroform층의 처리에 의한 apoptosis 유도는 caspase-3, 7, 9 및 PARP의 활성화와 연관성이 있었다.

• Nutrition Research and Practice
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• 제8권2호
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• pp.132-137
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• 2014

BACKGROUND/OBJECTIVES: In this study, the apoptogenic activity and mechanisms of cell death induced by hexane extract of aged black garlic (HEABG) were investigated in human leukemic U937 cells. MATERIALS/METHODS: Cytotoxicity was evaluated by MTT (3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide) assay. Apoptosis was detected using 4,6-diamidino-2-phenyllindile (DAPI) staining, agarose gel electrophoresis and flow cytometry. The protein levels were determined by Western blot analysis. Caspase activity was measured using a colorimetric assay. RESULTS: Exposure to HEABG was found to result in a concentration- and time-dependent growth inhibition by induction of apoptosis, which was associated with an up-regulation of death receptor 4 and Fas legend, and an increase in the ratio of Bax/Bcl-2 protein expression. Apoptosis-inducing concentrations of HEABG induced the activation of caspase-9, an initiator caspase of the mitochodrial mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase. HEABG also induced apoptosis via a death receptor mediated extrinsic pathway by caspase-8 activation, resulting in the truncation of Bid, and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. However, pre-treatment of U937 cells with the caspase-3 inhibitor, z-DEVD-fmk, significantly blocked the HEABG-induced apoptosis of these cells, and increased the survival rate of HEABG-treated cells, confirming that HEABG-induced apoptosis is mediated through activation of caspase cascade. CONCLUSIONS: Based on the overall results, we suggest that HEABG reduces leukemic cell growth by inducing caspase-dependent apoptosis through both intrinsic and extrinsic pathways, implying its potential therapeutic value in the treatment of leukemia.

• 생명과학회지
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• 제23권6호
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• pp.832-837
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• 2013

본 연구에서는 생체 내 구성요소 및 에너지원으로서 중요한 역할을 하는 글루타민 결핍에 의한 인체 전립선 PC3 암세포의 증식에 관한 기전 연구를 실시하였다. 글루타민 결핍에 의한 PC3 세포의 증식억제는 세포주기 G2/M arrest와 연관성이 있었으나, apoptosis 유발 현상은 관찰되지 않았다. 글루타민 결핍에 의한 G2/M arrest는 전사 및 번역 수준에서 Cdc2, cyclin A 및 cyclin B1의 발현 억제 및 p53 비의존적인 p21(WAF1/CIP1)의 발현 증가와 연관성이 있었다. 아울러 글루타민 결핍은 Chk1 및 Chk2의 인산화를 증가시켰으나, Cdc25C의 인산화는 감소시켰다. 본 연구의 결과는 글루타민 결핍에 의한 PC3 세포의 증식억제가 apoptosis 유발과는 상관없이 G2/M arrest를 유발시킨다는 첫 번째 증거이다.

• Biomolecules & Therapeutics
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• 제17권3호
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• pp.282-287
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• 2009

Ochnaflavone is a natural biflavonoid and mainly found in the caulis of Lonicera japonica (Caprifoliaceae). Biological activities such as anti-inflammatory and anti-atherogenic effects have been previously reported. The anticancer activity of ochnaflavone, however, has been poorly elucidated yet. In the present study, we investigated the effect of ochnaflavone on the growth inhibitory activity in cultured human colon cancer cell line HCT-15. Ochnaflavone inhibited the proliferation of the cancer cells with an $IC_{50}$ value of $4.1{\mu}M$. Flow cytometric analysis showed that ochnaflavone arrested cell cycle progression in the G2/M phase, and induced the increase of sub-G1 peak in a concentration-dependent manner. Induction of cell cycle arrest was correlated with the modulation of the expression of cell cycle regulating proteins including cdc2 (Tyr15), cyclin A, cyclin B1 and cyclin E. The increase of sub-G1 peak by the higher concentrations of ochnaflavone (over $20{\mu}M$) was closely related to the induction of apoptosis, which was evidenced by the induction of DNA fragmentation, activation of caspase-3, -8 and -9, and cleavage of poly-(ADP-ribose) polymerase. These findings suggest that the cell cycle arrest and induction of apoptosis might be one possible mechanism of actions for the anti-proliferative activity of ochnaflavone in human colon cancer cells.

• 한방재활의학과학회지
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• 제21권2호
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• pp.1-13
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• 2011

Objectives : We investigated the effect of Haein-tang(Hairen-tang) on short-term memory and apoptosis in dentate gyrus of the gerbils with transient global ischemia. Methods : For the induction of cerebral ischemia model in mice, common carotid arteries of gerbils were occluded with aneurysm clips for 5 min. One day after operation, Haein-tang(Hairen-tang) was administrated orally injected once a day for 15 consecutive days. Gerbils were randomly divided into four group(n=10 in each group): sham-operation group, ischemia-induction group, ischemia-induction and 50 mg/kg Haein-tang(Hairen-tang)-treated group, ischemia-induction and 100 mg/kg Haein-tang(Hairen-tang)-treated group, and ischemia-induction and 200 mg/kg Haein-tang(Hairen-tang)-treated group. The effect of Haein-tang(Hairen-tang) on memory function was investigated by using step-down avoidance task. Apoptosis was confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining and immunohistochemistry for caspase-3. Western blot analysis for the expressions of Bax and Bcl-2 protein was also conducted. Results : 1. Haein-tang extract significantly enhanced short-term memory in step-down avoidance task and 100 mg/kg, 200 mg/kg Haein-tang-treated group. 2. Haein-tang extract significantly suppressed TUNEL-positive cells after transient global ischemia and 50 mg/kg, 100 mg/kg, 200 mg/kg Haein-tang-treated group. 3. Haein-tang extract significantly increased caspase-3 positive cells in the hippocampal dentate gyrus after transient global ischemia and 50 mg/kg, 100 mg/kg, 200 mg/kg Haein-tang-treated group. 4. Haein-tang extract significantly decreased Bax protein expressions in the hippocampus after transient global ischemia and 100 mg/kg, 200 mg/kg, Haein-tang-treated group. Haein-tang extract significantly increased Bcl-2 protein expressions in the hippocampal dentate gyrus after transient global ischemia and 50 mg/kg, 100 mg/kg, 200 mg/kg, Haein-tang-treated group. Haein-tang extract significantly decreased Ratio of Bax protein to Bcl-2 protein in the hippocampus after transient global ischemia and 100 mg/kg, 200 mg/kg Haein-tang-treated group. Conclusions : While Haein-tang(Hairen-tang) treatment improved short-term memory by suppressing on ischemia-induction apoptosis. In the present study, Haein-tang(Hairen-tang) shows protective effect on transient global ischemia.

• 생명과학회지
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• 제25권1호
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• pp.93-100
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• 2015

Pachymic acid는 복령에서 분리된 lanostane-type인 triterpenoid의 일종이다. 최근 pachymic acid가 항암 및 항염증 효능과 산화적 스트레스에 대한 항산화 효능 등과 같은 약리적인 효능이 있는 것으로 밝혀지고 있으나, 그에 대한 구체적인 분자생물학적 기전 연구는 매우 미비한 실정이다. 본 연구에서는 pachymic acid의 항암활성 및 관련 기전 조사의 일환으로 T24 인체 방광암세포 모델을 이용하여 pachymic acid에 의한 apoptosis 유발 여부를 검증하였다. 본 연구의 결과에 의하면 pachymic acid는 T24 세포의 증식을 유의적으로 억제시켰으며, 이는 apoptosis 유발과 연관성이 있음을 다양한 방법으로 확인하였다. Pachymic acid에 의한 apoptosis 유도에는 pro-apoptotic 인자들의 발현 증가와 anti-apoptotic 유전자 산물들의 발현 감소가 동반되었으며, MMP의 소실과 tBid의 발현 증가가 관찰되었다. 아울러 pachymic acid는 extrinsic 및 intrinsic apoptosis 경로의 개시에 관여하는 caspase-8 및 -9의 활성뿐 만 아니라, caspase-3의 활성도 증가시킴으로서 PARP와 같은 기질 단백질의 단편화를 초래하였다. 따라서 pachymic acid는 항암활성을 지니는 천연생리활성 물질로서의 잠재력이 매우 높음을 알 수 있었다.