• 대한한방부인과학회지
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• 제19권2호
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• pp.92-106
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• 2006

Purpose : To address the ability of Olibanum to induce cell death, we investigated the effect of olibanum on cell apoptosis. Twenty-four hours later, apoptosis occurred following olibanum exposure in a dose-dependent manner. Methods : We culture HeLa cell which is human metrocarcinoma cell in D-MEM included 10% fetal bovine serum(Hyclone Laboratories) below $37^{\circ}C$, 5% CO2. Then we observed apoptosis of log phage cell which is changed cultivation liquid 24 Hours periodically. Results : The treatment of BAPTA-AM regulated olibanum-induced apoptosis in HeLa human cervical carcinoma cells. The 24 hr-earlier -thapsigargin-pretreated cell showed the resistance against olibanum-induced apoptosis and the Ru360-mitochondrial uniporter-inhibited olibanum-induced apoptosis, too. It means that olibanum leads to the accumulation of calcium and the resultant apoptosis in HeLa cells. Immunoblotting data also shows that the expression of GRP78, ER stress marker protein, was induced by the olibanum. Bcl-2, anti-apototic protein, was decreased and that the expression of Bax, pro-apoptotic protein, was increased by the addition of olibanum. Interestingly, the olibanum increased the activity of caspase-8 as well as calpain cysteine pretense in HeLa cervical carcinoma cells. Calpain inhibitor-calpastatin as well as caspase-8C/A expression abrogated olibanum-induced apoptosis in the carcinoma cells. The inhibition of caspase-8 regulated olibanum-induced calpain activation but the inhibition of calpain did not have any effect on the caspase-8 activation in HeLa human cervical carcinoma cells. Conclusion : We conclude that olibanum induces the accumulation of calcium and the resultant apoptosis in which caspase-8 and calpain are involved.

• 생명과학회지
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• 제17권6호통권86호
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• pp.766-771
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• 2007

B형 간염 바이러스(HBV)와 C형 간염 바이러스(HCV)에 함께 감염되면 단독 감염의 경우보다 더 심각한 간질환이 유발되고 간암으로의 발전 가능성도 높아진다. 본 연구에서는 HBV의 X단백질(HBx)과 HCV의 코어 단백질이 인간 간암세포주인 HepG2세포에서 p53의 양을 협조적으로 증가시킨다는 것을 보여 주었다. 이로 인하여 세포예정사를 촉진하는 Bax 단백질의 발현이 더 증가하는 반면에 세포예정사를 억제하는 Bcl2의 발현은 더 억제됨이 관찰되었다. 그러나 이러한 효과들은 p53-음성인 Hep3B 세포에서는 관찰되지 않았다. 나아가 HBx와 코어 단백질은 HepG2의 cisplatin-매개성 세포예정사를 협조적으로 증가시키는 반면에 Hep3B에서는 이러한 효과가 나타나지 않았다. 이러한 연구 결과들은 HBV와 HCV가 동시에 감염되었을 경우에 나타나는 임상적인 소견을 이해하고 세포예정사에 미치는 HBx와 코어 단백질의 영향에 대한 기존의 상충적인 연구결과들을 해석하는데 도움을 줄 수 있다.

• 동의생리병리학회지
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• 제20권6호
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• pp.1548-1555
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• 2006

Bujeonghangam-tang(BHT) has been used as an anticancer agent in oriental medicine, but the mechanism by which it induces cell death in cancer cells is still unclear. To investigate cell death mechanism by BHT in cancer cells, the activities of apoptosis signaling pathway were tested in human neuroblastoma cell line LAN5. Viability of LAN5 cells was markedly decreased by treatment of the water extract of BHT in a dose-dependent manner. BHT induced cell death was confirmed as apoptosis characterized by chromatin condensation. We tested whether the water extract of BHT affects the anti-apoptotic protein such as Bcl-2 and Bcl-XL, and the pro-apoptotic protein such as Bax. Both Bcl-2 and Bcl-XL were gradually decreased but Bas was increased in a time-dependent manner after the addition of the water extract of BHT. Cleavage of Bid by activation of caspase-8 protease was also observed in LAN-5 cells by the treatment of the water extract of BHT. Taken together, these results suggest that the water extract of BHT exerts anti-cancer effects on human neuroblastoma LAN-5 cells by inducing the apoptotic death via down-regulation of anti-apoptotic proteins such as Bcl-2 and Bcl-XL, up-regulation of pro-apoptotic protein such as Bax, and activation of intrinsic caspase cascades.

• 동의생리병리학회지
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• 제30권3호
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• pp.150-156
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• 2016

Extract of Broussometia kazinoki Rhizodermatis has been traditionally used for geopoong, diuresis, hwalhyeol. In the present study, the apoptotic effect of methanol extract of Broussometia kazinoki (MBK) were investigated. Cell viability of A549 cells was measured by MTT assay. Apoptosis-related protein and MAPK protein levels were measured by Western blot. Chromatin condensation of A549 cells was stained with DAPI. MBK inhibited cell proliferation of A549 cell. Based on DAPI staining, MBK-treated cells manifested nuclear shrinkage, condensation and fragmentation. Treatment of A549 cells with MBK resulted in activation of the caspase-3, -8, -9 and cleavage of poly ADP-ribose polymerase (PARP). In the upstream, MBK increased the expressions Bax and Bak, decreased the expression of Bcl-2, and augmented the Bax/Bcl-2 ratio. MBK-induced apoptosis was accompanied by sustained phosphorylation of JNK, p38 MAPK and apoptosis signal-regulating kinase (ASK)-1. These results suggest that MBK induced apoptosis in A549 cells through Bcl-2 family protein-mediated mitochondria/caspase-3 dependent pathway. In addition, MBK increased the activation of ASK-1, which are critical upsteam signals for JNK/p38 MAPK activation in A549 cancer cells.

• BMB Reports
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• 제52권11호
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• pp.665-670
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• 2019

Nucleotide-binding oligomerization domain protein 2 (NOD2), an intracellular pattern recognition receptor, plays important roles in inflammation and cell death. Previously, we have shown that NOD2 is expressed in vascular smooth muscle cells (VSMCs) and that NOD2 deficiency promotes VSMC proliferation, migration, and neointimal formation after vascular injury. However, its role in endoplasmic reticulum (ER) stress-induced cell death in VSMCs remains unclear. Thus, the objective of this study was to evaluate ER stress-induced viability of mouse primary VSMCs. NOD2 deficiency increased ER stress-induced cell death and expression levels of apoptosis mediators (cleaved caspase-3, Bax, and Bak) in VSMCs in the presence of tunicamycin (TM), an ER stress inducer. In contrast, ER stress-induced cell death and expression levels of apoptosis mediators (cleaved caspase-3, Bax, and Bak) were decreased in NOD2-overexpressed VSMCs. We found that the $IRE-1{\alpha}-XBP1$ pathway, one of unfolded protein response branches, was decreased in NOD2-deficient VSMCs and reversed in NOD2-overexpressed VSMCs in the presence of TM. Furthermore, NOD2 deficiency reduced the expression of XBP1 target genes such as GRP78, PDI-1, and Herpud1, thus improving cell survival. Taken together, these data suggest that the induction of ER stress through NOD2 expression can protect against TM-induced cell death in VSMCs. These results may contribute to a new paradigm in vascular homeostasis.

• Journal of Microbiology and Biotechnology
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• 제32권4호
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• pp.493-503
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• 2022

Forkhead transcription factor 3a (Foxo3a) is believed to be a tumor suppressor as its inactivation leads to cell transformation and tumor development. However, further investigation is required regarding the involvement of the activating transcription factor 3 (ATF3)-mediated Tat-interactive protein 60 (Tip60)/Foxo3a pathway in cancer cell apoptosis. This study demonstrated that Chelidonium majus upregulated the expression of ATF3 and Tip60 and promoted Foxo3a nuclear translocation, ultimately increasing the level of Bcl-2-associated X protein (Bax) protein. ATF3 overexpression stimulated Tip60 expression, while ATF3 inhibition by siRNA repressed Tip60 expression. Furthermore, siRNA-mediated Tip60 inhibition significantly promoted Foxo3a phosphorylation, leading to blockade of Foxo3a translocation into the nucleus. Thus, we were able to deduce that ATF3 mediates the regulation of Foxo3a by Tip60. Moreover, siRNA-mediated Foxo3a inhibition suppressed the expression of Bax and subsequent apoptosis. Taken together, our data demonstrate that Chelidonium majus induces SKOV-3 cell death by increasing ATF3 levels and its downstream proteins Tip60 and Foxo3a. This suggests a potential therapeutic role of Chelidonium majus against ovarian cancer.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.256.1-256.1
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• 2002

We investigated the anti-proliferative effects of a new compound. ircinin-1. from the sponge Sarcotragus sp. on SK-MEL -2 human skin cancer cells. From the data of MTT assay, cell viability was decreased by ircinin-1 in a dose-dependent manner. We observed that the anti-proliferative effect of ircinin-1 was due to the induction of apoptosis, which was confirmed by observing the morphological changes. the increased ratio of pro-apoptotic protein Bax to anti-apoptotic protein Bcl-2, and cleavage of poly(ADP-ribose) polymerase protein, via activation of caspase-3. (omitted)

• 한국식품영양과학회지
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• 제31권6호
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• pp.1126-1133
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• 2002

CLA 이성체 mixture와 trans-10,cis-12 CLA는 살아있는 TSU-Prl 세포 수를 감소시키는 반면 LA와 cis-9,trans-11 CLA는 세포 수에 아무런 효과가 없었다. 세포 수를 감소시키는 CLA 이성체 mixture와 tran-10, cis-12 CLA는 apoptotic cell death를 유도하는 것을 관찰하였고, 특히 trans-10,cis-12 CLA는 Bcl-2/Bax 비율을 감소시켰다. Trans-10,cis-12 CLA에 의해 Bax와 Bcl-2 mRNA의 수준이 변하지 않았으므로 이 지방산에 의한 Bcl-2의 변화는 mRNA 전사 후에 일어나는 단계에서 일어난다고 결론지을 수 있다. 이로써 CLA에 의한 세포증식 억제는 부분적으로 TSU-Prl 세포의 apoptosis를 유도함으로서 이루어지는 것이라 할 수 있다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.166.2-166.2
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• 2003

Garlic (Allium sativum) has been used as a general food and a remedy in Oriental for a long time. Since garlic compounds have been also shown to inhibit growth of tumors and to modulate the activity of carcinogenesis, the effects of allicin on growth and survival in human gastric epithelial cells were evaluated by cell viability, cell cycle analysis and DNA fragmentation. Protein levels of cytochrome C, Bcl-xL, Bax and AIF were detected by Western blotting. Effects of recombinant VacA on caspase proteases activity were also determined. (omitted)

• Environmental Analysis Health and Toxicology
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• 제19권3호
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• pp.321-326
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• 2004

The study of p53 tumor suppressor protein is one of most important subjects in an environmental toxicology as well as in cancer biology. Generally, p53 has been known to involve the cell cycle regulation and apoptosis by the activation of its target genes such as p21 and bax in a number of cellular stress responses. In addition, associations of p53 with cellular proteins presumably reflect the involvement of p53 in critical cellular processes such as DNA repair. The complex formation of p53 and exogenous proteins such as viral or cellular proteins has been shown in many cases to play important roles in carcinogenic processes against environmental mutagen. Recently, the disruption of p53 protein by oxidative stress has been also reported to have relevance to carcinogenesis. These findings suggested that the maintaining of stability and functional activity of p53 protein was also important aspect to play as a tumor suppressor protein. Therefore, the detection of functional status of p53 proteins might be an effective biomarker for the cancer and human diseases under the environmental toxicologic carcinogen.