• 동의생리병리학회지
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• 제17권1호
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• pp.85-90
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• 2003

We investigated the effects of Oak smoke flavoring (OSF, Holyessing) on the growth of DU145 and PC-3 human prostate carcinoma cells. OSF treatment resulted in a concentration-dependent growth inhibition in both DU145 and PC3 cell lines. The anti-proliferative effect of OSF treatment was associated with the induction of apoptotic cell death which was confirmed by morphological change such as membrane shrinking, rounding up and chromatin condensation in DU145 and PC-3 cells. DNA flow cytometry analysis confirmed that OSF treatment increased population of apoptotic sub-G1 phase. Furthermore, we observed an increase of pro-apoptotic protein Bax expression and a decrease of anti-apoptotic protein Bcl-2 by OSF treatment in a dose-dependent manner. OSF also induced a proteolytic cleavage of specific target proteins such as poly(ADP-ribose) polymerase (PARP) and β-catenin proteins. The present results indicated that OSF-induced inhibition of human prostate carcinoma cell proliferation is associated with the induction of apoptosis.

• 동의생리병리학회지
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• 제17권3호
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• pp.751-758
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• 2003

In our previous studies, we reported that Selaginella Tamariscina(ST) induced apoptotic cell death in HL-60 cells selectively. The cell viability after treatment with extract of ST was quantified by MTT assay and trypan bleu exclusion method. The results showed that application with ST in HL-60 induced 40% cell death at the concentration of 400 ㎍/ml. The cancericidic effect of Selaginella Tamariscina was mediated by apoptosis. Thus, HL-60 cells exposed to Selaginella Tamariscina displayed the DNA fragmentation ladder and nucleus chromatin condensation characteristic for apoptosis. The enzyme activity of caspase-3 and actived caspase-3 protein were markedly increased in HL-60 cells treated with the extract of Selaginella Tamariscina. In addition, the extract of Selaginella Tamariscina induced cleavage of PARP, a known substrate for caspase-3. The expression of Bcl-2, anti-apoptotic protein, was decreased by treatment of the aqueous extract of Selaginella Tamariscina in a dose-dependent manner. And the expression of pro-apoptotic Bax protein was increased. In conclusion, our results suggest that the extract of Selaginella Tamariscina may induce the apoptotic death of HL-60 cells via activation of caspase-3, cleavage of PARP protein, depletion of cellular ATP levels and Bcl-2 degradation.

• BMB Reports
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• 제50권1호
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• pp.43-48
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• 2017

Accumulation of tissue macrophages is a significant characteristic of disease-associated chronic inflammation, and facilitates the progression of disease pathology. However, the functional roles of these bone marrow-derived macrophages (BMDMs) in aging are unclear. Here, we identified age-dependent macrophage accumulation in the bone marrow, showing that aging significantly increases the number of M1 macrophages and impairs polarization of BMDMs. We found that age-related dysregulation of BMDMs is associated with abnormal overexpression of the anti-inflammatory interleukin-10. BMDM dysregulation in aging impairs the expression levels of pro-inflammatory cytokines and genes involved in B-cell maturation and activation. Phagocytosis of apoptotic Jurkat cells by BMDMs was reduced because of low expression of phagocytic receptor CD14, indicating that increased apoptotic cells may result from defective phagocytosis of apoptotic cells in the BM of aged mice. Therefore, CD14 may represent a promising target for preventing BMDM dysregulation, and macrophage accumulation may provide diagnostic and therapeutic clues.

• The Korean Journal of Physiology and Pharmacology
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• 제5권5호
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• pp.381-388
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• 2001

This work describes the pharmacological inhibition by KR 31378 and its acetyl metabolite, KR 31612, of the apoptotic cell death induced by $H_2O_2$ in the A7r5 cells. Exposure of A7r5 cells to $H_2O_2$ (0.5 mM) induced a concentration-dependent cytotoxicity in association with oligonucleosomal DNA fragmentation. $H_2O_2-induced$ cell death was potently suppressed by KR 31378, KR 31612, ${\alpha}-tocopherol$ or trolox. Additionally, the apoptotic death of A7r5 cells (DNA ladders on electrophoresis) was also strongly suppressed by KR 31378 and KR 31612, but to a less degree by ${\alpha}-tocopherol$ and trolox. As a mechanistic study, incubation with $H_2O_2$ markedly showed a decreased Bcl-2 level and, in contrast, increased Bax protein and cytochrome C release, which were significantly and concentration-dependently reversed by KR 31378 and KR 31612 as well as by ${\alpha}-tocopherol$ and trolox. KR 31378 and ${\alpha}-tocopherol$ significantly reduced lipid peroxidation in accordance with reduced intracellular ROS and peroxyl radical. These results suggest that KR 31378 has a therapeutic potential against the apoptotic injury via mediation of anti- oxidative stress.

• 동의생리병리학회지
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• 제17권2호
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• pp.451-456
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• 2003

We investigated the effects of Sabaek-san (SBS) water extract on the growth of human lung carcinoma A549 cells. Upon treatment with SBS extract, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis. including condensation of chromatin. Flow cytometry analysis confirmed that SBS treatment increased populations of apoptotic-sub G1 phase. In addition. proteolytic cleavages of poly(ADP-ribose) polymerase and β-catenin protein were observed after treatment of SBS extract. These apoptotic effects of SBS in A549 cells were associated with marked inhibition of Bcl-2 and Bel-xL mRNA in a dose-dependent manner. however the levels of Bax expression were not affected, SBS treatment also induced a proteolytic activation of caspase-3. which is believed to play a central role In the apoptotic signaling pathway. The previous and present results indicated that SBS-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1/S progression and the induction of apoptosis.

• 동의생리병리학회지
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• 제19권6호
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• pp.1552-1556
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• 2005

Silymarin has been known to exert anti-tumoral activity in Korea. However, its molecular mechanism of action is not understood. In this study, we found that silymarin induced apoptosis in androgen-independent prostate cancer DU145 cells as confirmed by DNA fragmentation. Our data demonstrated that silymarin-induced apoptotic cell death was accompanied by activation of caspase-3 and subsequent cleavages of its substrates, poly(ADP-ribose) polymerase (PARP) in a time- and concentration-dependent manner. Also, silymarin-induced apoptotic mechanism of DU145 cells involved the induction of Par-4 protein expression. Taken together, these results suggest that silymarin induces the activation of caspase-3, degradation of PARP, increase of Par-4 expression, and eventually leads to apoptotic cell death.

• 동의생리병리학회지
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• 제19권3호
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• pp.722-728
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• 2005

The DNA topoismerase I inhibitor ${\beta}-lapachone$, the product of a lapacho tree (Tabebuia avellanedae) from South America, activates a novel apoptotic response in a number of cell lines. In the present report, we investigated the effects of ${\beta}-lapachone$ on the growth of human lung in human non-small-cell-lung-cancer A549 cells. Upon treatment with ${\beta}-lapachone$, a concentration-dependent inhibition of cell viability and cell proliferation was observed as measured by hemocytometer counts and MTT assay. The ${\beta}-lapachone-treated$ cells developed many of the hallmark features of apoptosis, including membrane shrinking, condensation of chromatin and DNA fragmentation. These apoptotic effects of ${\beta}-lapachone$ in A549 cells were associated with a marked induction of pro-apoptotic Bax expression, however the levels of anti-apoptotic Bcl-2 expression were decreased in a dose-dependent manner. Accordingly, elevated amount of cyclin-dependent kinase inhibitor p21 expression accompanied by up-regulation of tumor suppressor p53 was observed. By RT-PCR analyses, decrease in gene expression level of telomerase reverse transcriptase and telomeric repeat binding factor were also observed. Thus, these findings suggest that ${\beta}-lapachone$ may be a potential anti-cancer therapeutics for the control of human lung cancer cell model.

• Molecules and Cells
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• 제38권2호
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• pp.145-150
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• 2015

Continuous intra- and extracellular stresses induce disorder of $Ca^{2+}$ homeostasis and accumulation of unfolded protein in the endoplasmic reticulum (ER), which results in ER stress. Severe long-term ER stress triggers apoptosis signaling pathways, resulting in cell death. Neural epidermal growth factor-like like protein 2 (NELL2) has been reported to be important in protection of cells from cell death-inducing environments. In this study, we investigated the cytoprotective effect of NELL2 in the context of ER stress induced by thapsigargin, a strong ER stress inducer, in Cos7 cells. Overexpression of NELL2 prevented ER stress-mediated apoptosis by decreasing expression of ER stress-induced C/EBP homologous protein (CHOP) and increasing ER chaperones. In this context, expression of anti-apoptotic Bcl-xL was increased by NELL2, whereas NELL2 decreased expression of pro-apoptotic proteins, such as cleaved caspases 3 and 7. This anti-apoptotic effect of NELL2 is likely mediated by extracellular signal-regulated kinase (ERK) signaling, because its inhibitor, U0126, inhibited effects of NELL2 on the expression of anti- and pro-apoptotic proteins and on the protection from ER stress-induced cell death.

• 한국식품영양과학회지
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• 제38권5호
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• pp.644-648
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• 2009

Bacillus subtilis로 발효한 두유의 암세포 증식 저해 효과를 알아보기 위하여 AGS 인체 위암 세포를 이용하여 실험을 수행하였다. 두유와 발효두유 모두 암세포 성장 저해 효과가 나타났으며, 발효두유에서 그 효과가 더욱 증진되었다. 이러한 결과는 apoptosis에 의해 암세포 증식이 저해된 것으로 사료되며 DAPI staining을 통해 뚜렷한 apoptotic body를 관찰할 수 있었다. 발효두유를 처리한 암세포에서 apoptosis를 유발하는 인자인 bcl-2의 발현은 감소하고, 억제하는 인자인 bax의 발현은 발효하지 않은 두유보다 상대적으로 증가하였다. 또한 종양억제 유전자인 p53과 p21의 발현 역시 발효하지 않은 두유보다 발효두유에서 더 증가되었다. 따라서 발효두유의 항암 효과는 이들 유전자의 발현을 조절하여 유도된 apoptosis에 의한 것으로 보이며, 발효두유와 발효하지 않은 두유의 항암효과의 차이는 발효 균주와 발효과정중 생성된 여러 가지 발효산물들이 암세포 성장 억제에 영향을 끼친 것으로 생각된다.

• 한국식품영양과학회지
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• 제31권3호
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• pp.521-526
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• 2002

대두(백태,흑태)와 현미의 메탄올과 아세톤 추출물이 호르몬 의존형 유방암세포(MCF-7)와 호르몬 비의존형세포(MDA-MB-231)의 세포독성과 apoptosis에 미치는 영향을 살펴보았다 각 추출물별 25, 50, 100 ug/well의 농도로 24, 48, 72시간 배양 시 배양시간과 사용된 시료 모두 농도 의존적으로 유방암 세포생존율을 억제하는 것으로 나타났다. 특히 호르몬 의존형 세포인 MCF-7 에서는 현미의 아세톤 추출물이 낮은 농도에서 짧은 배양시간에도 그 효과가 나타났고 호르몬 비의존형 세포주 MDA-MB-231에서는 현미의 아세톤 및 메탄올 추출물의 효과가 다른 시료들에 비해 높게 나타났다. Apoptosis에 미치는 영향에서는 호르몬 비의존형 세포(MDA-MB-231)에서 메탄올추출물 처리군이 대조군에 비해 apoptosis된 세포가 유의적으로 증가한 것을 관찰할 수 있었다. 그러나 세포생존율 결과와는 다르게 호르몬의존형 세포와 호르몬비의존형 세포 모두에서 아세톤 처리군은 대조군에 비해 apptosis에 유의차를 나타내지 않았다. 이상의 결과에 의하면 이들 화합물이 소유한 암세포 성장억제 기전은 추출물내 함유된 화합물의 종류와 세포성장의 호르몬 의존도에 따라 다양한 것으로 사료된다.