• BMB Reports
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• 제47권8호
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• pp.433-438
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• 2014

Plant sterols have shown potent anti-proliferative effects and apoptosis induction against breast and prostate cancers. However, the effect of sterols against hepatic cancer has not been investigated. In the present study, we assessed whether the stigmasterol isolated from Navicula incerta possesses apoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the results, Stigmasterol has up-regulated the expression of pro-apoptotic gene expressions (Bax, p53) while down-regulating the anti-apoptotic genes (Bcl-2). Probably via mitochondrial apoptosis signaling pathway. With the induction of apoptosis caspase-8, 9 were activated. The DNA damage and increase in apoptotic cell numbers were observed through Hoechst staining, annexin V staining and cell cycle analysis. According to these results, we can suggest that the stigmasterol shows potent apoptosis inductive effects and has the potential to be tested as an anti-cancer therapeutic against liver cancer.

• 동의신경정신과학회지
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• 제10권2호
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• pp.47-57
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• 1999

Recently, essential oils are used for aromatherapy. Most essential oils are said to be anti-bacterial; some may be anti-viral or anti-fungal. I investigated the effects of peppermint pure essential oil on the heat shock-induced apoptosis in human astrocyte cell line CCF-STTGI. In previous studies, heat shock has been reported to induce the apoptosis or programmed cell death through the activation of caspase-3. We studied the heat shock-induced apoptosis through flow cytometry, DNA electrophoresis, and giemsa staining. Interestingly, these events were inhibited by pretreatment of peppermint pure essential oils in CCF-STTGl cells. Peppermint oil also inhibited the heat shock-induced apoptosis in primary cultured rat astrocytes. In addition, this Peppermint essential oil inhibited the heat shock-induced activation of caspase-3. These results suggest that peppermint pure essential oils may modulate the apoptosis through the activation of the interleukin-I -converting enzyme-like protease.

• Biomolecules & Therapeutics
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• 제21권5호
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• pp.364-370
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• 2013

Resveratrol (trans-3,4'-trihydroxystillbene), a naturally occurring polyphenolic antioxidant found in grapes and red wine, elicits diverse biochemical responses and demonstrates anti-aging, anti-inflammatory, and anti-proliferative effects in several cell types. Previously, resveratrol was shown to regulate differentiation and inflammation in rabbit articular chondrocytes, while the direct production of nitric oxide (NO) in these cells by treatment with the NO donor sodium nitroprusside (SNP) led to apoptosis. In this study, the effect of resveratrol on NO-induced apoptosis in rabbit articular chondrocytes was investigated. Resveratrol dramatically reduced NO-induced apoptosis in chondrocytes, as determined by phase-contrast microscopy, the MTT assay, FACS analysis, and DAPI staining. Treatment with resveratrol inhibited the SNP-induced expression of p53 and p21 and reduced the expression of procaspase-3 in chondrocytes, as detected by western blot analysis. SNP-induced degradation of I-kappa B alpha ($I{\kappa}B-{\alpha}$) was rescued by resveratrol treatment, and the SN50 peptide-mediated inhibition of NF-kappa B (NF-${\kappa}B$) activity potently blocked SNP-induced caspase-3 activation and apoptosis. Our results suggest that resveratrol inhibits NO-induced apoptosis through the NF-${\kappa}B$ pathway in articular chondrocytes.

• Molecules and Cells
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• 제28권6호
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• pp.509-513
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• 2009

Here, we show that JNK1 and JNK3 have different roles in ${\alpha}-$ or etoposide-induced apoptosis in HeLa cells. Dominant negative JNK1 inhibited $TNF-{\alpha}-$ or etoposide-induced apoptosis, while dominant negative JNK3 promoted $TNF-{\alpha}-$ or etoposide-induced apoptosis. During $TNF-{\alpha}$-induced apoptosis, JNK1 was activated in a biphasic manner, exhibiting both transient and sustained activity, whereas JNK3 was activated early and in a transient manner. The role of JNK3 activation was an anti-apoptotic effect, while the role of JNK1 activation was a pro-apoptotic effect. These results suggest that the anti-apoptotic mechanism of JNK3 in $TNF-{\alpha}$-induced apoptosis originates before the apoptotic machinery is triggered.

• 생명과학회지
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• 제24권9호
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• pp.1012-1018
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• 2014

제주조릿대(Sasa quelpaertensis Nakai)는 한라산에 넓게 분포되어 자생하는 식물로 최근 연구에서 항염증, 항당뇨, 항산화, 항암 효능을 가지는 것으로 알려져 있으나 대장암에서의 항암 효능 및 그에 따른 mechanism에 대해서는 명확히 밝혀지지 않았다. 본 연구에서는 인간 대장암 HT-29 세포를 대상으로 제주조릿대에 의한 항암작용과 기전에 대해 조사하였다. 제주조릿대에 의한 HT-29 세포의 증식 억제가 apoptosis 유도와 연관성이 있음을 DNA fragmentation와 flow cytometry 분석에 의한 sub-G1기의 세포빈도의 증가로 확인하였다. 제주조릿대에 의한 apoptosis 유발은 HT-29 세포의 S arrest 현상을 동반하였을 뿐만 아니라 발생한 산화질소의 증가와 anti-apoptotic factor인 IAP family (survivin, XIAP, cIAP-1, cIAP-2) 발현이 감소함으로써 촉진되었음을 확인할 수 있었다. 이러한 결과들은 제주조릿대가 대장암에 대한 치료제로서의 사용 가능성을 확인할 수 있었지만 이를 입증하기 위해서는 더 자세한 항암기전에 관한 연구가 진행되어야 한다고 사료된다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2002년도 생물공학의 동향 (X)
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• pp.62-65
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• 2002

We have previously shown that the addition of silkworm hemolymph to a culture medium increases the longevity of insect and mammalian cells by inhibiting apoptosis. This indicates that the component which inhibits apoptosis is contained in the silkworm hemolymph, The apoptosis-inhibiting component was isolated from silkwonn hemolymph and characterized in our previous study. A database search using the N-terminal amino acid sequence of this component as a template resulted in a 95% homology with a low molecular weight lipoprotein, the so called ’30K protein' of unknown function. In this study, the 30K protein gene was expressed in mammalian and insect cells to confirm the apoptosis-inhibiting effect. The overexpression of 30K protein in mammalian cell inhibited the staurosporin-induced apoptosis by the prevention of the activation of caspase 3. Using an Autographa californicanuclear polyhedrosis virus (AcNPV) system, the 30K protein was overexpressed also in insect cells. The expression of the 30K protein increased the longevity of baculovirus-infected insect cells by inhibiting apoptosis. These results suggest that the 30K protein is a novel anti-apoptotic protein.

• 동의생리병리학회지
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• 제26권4호
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• pp.519-526
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• 2012

Recently, herbal flavonoids have been implicated for anti-cancer therapy. Flavonoids as a commonly known for their anti-oxidant activity, are contained in the herbal medicine as well as root of plants, vegetables, fruits, grains, tea, and wine. Kaempferol, a component of Polygonati rhizoma, a member of the herbal flavonoids, has been studied for anti-hypercholesterol, anti-hypertension and anti-diabetes. It is also known to be effective in anti-cancer therapy for breast, prostate and other type of cancers. However, the anti-cancer therapeutic mechanisms are pooly understood. Here, we investigated the molecular mechanism underlying kaempferol-induced anti-cancer effects using the human liver cancer cell lines, Hep3B, HepG2, and Sk-Hep-1, and human Chang liver cell as a control. As shown by the FACS analysis, measurement of caspase activity, DAPI and trypan blue staining, and DNA fragmentation assay, kaempferol induced apoptosis in the liver cancer cells with the greater potential in Hep3B cells than other liver cancer cells. In addition, we performed microarray analysis to profile the genome-wide mRNA expression regulated by kaempferol. Many of the apoptosis-related genes were significantly induced in kaempferol-treated Hep3B cells, in particular, the genes associated with MAPK cascade. Additionally, kaempferol induced the mRNA expression of genes involved in MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathway, which are all known to trigger apoptosis. Overall, our data suggest that kaempferol has anti-liver cancer effects by inducing apoptosis through the MKK7-JNK cascade, MKK3-p38 cascade, and caspase signaling pathways.

• 대한한의학방제학회지
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• 제10권1호
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• pp.143-155
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• 2002

In the hope of identifying anti-leukemic agents from traditional herbal medicines. this study was designed to investigate the anti-leukemic effects of the herbal medicine Jipaesan, which is composed of Angelica Dahurica and Fritillariae Verticillata. in acute promyeloid leukemia HL-60 cells. Jipaesan showed anti-proliferative effect through the induction of differentiation and apoptosis in HL -60 cells. Verticinone as a major differentiating agent and imperatorin as major apoptosis-inducing agent were isolated from the water extracts of F. Verticillata and A. Dahurica, respectively. Combined treatment of HL-60 cells with two major compounds showed synergy in the induction of differentiation. Since the induction of differentiation and/or apoptosis has therapeutic values in curing acute leukemic diseases. Jipaesan could be useful as an anti-leukemic agent.

• 대한본초학회지
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• 제22권2호
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• pp.65-72
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• 2007

Objectives : In this study, we investigate that Euphorbiae lathyridis Semen extract contributes to growth inhibitory effect and anti-cancer activity on the HT-29 human colon cancer cells. Methods : Euphorbiae lathyridis Semen was extracted from the Semen of the plant using 80% Methanol. The Euphorbiae lathyridis Semen extract was treated to different concentrations for 24 hr, 4Shr or 72hr. Growth inhibitory effect was analyzed by measuring FACS study and MTT assay. Cell apoptosis was confirmed by surveying caspases cascades activation using Westem blot. Results : Exposure to Euphorbiae lathyridis Semen extract (0.4mg/ml) results in an inhibitory effect on cell growth in HT-29 cells. Growth inhibition by Euphorbiae lathyridis Semen extract in HT-29 cells was related with the inhibition of proliferation and induction of apoptosis. The Euphorbiae lathyridis Semen extract induces DNA fragmentation in HT-29 cells. Furthermore, Euphorbiae lathyridis Semen extract induces cell apoptosis through the activation of caspases-3, caspase-9 and PARP cleavage. Conclusion : Euphorbiae lathyridis Semen extract induces apoptosis in human colon cancer cells, therefore, we suggest that Euphorbiae lathyridis Semen extract can be used as a novel class of anti-cancer drugs.

• 대한한의학회지
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• 제36권4호
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• pp.19-34
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• 2015

Objectives: This study was performed to investigate the anti-tumor effect of O. japonicus extracts on intrahepatic cholangiocarcinoma cell line SNU-1079. Methods: Cholangiocarcinoma SNU-1079 cells were treated with various concentrations of O. japonicus DW and EtOH extracts ($0-300{\mu}g/ml$) for 24, 48 or 72 h. Cell viability was evaluated through a PMS/MTS assay, and the apoptosis rate was examined through ELISA assay and flow cytometry analysis. The mRNA expression of apoptosis- and cell cycle progression-related genes (Bcl-2, Mcl-1, Bax, Survivin, Cyclin D1, and p21) was evaluated using real-time PCR, and the caspase activity was examined using immunoblot analysis. Results: O. japonicus extracts inhibited cell proliferation and increased apoptosis rate in both ELISA assay and flow cytometry analysis. O. japonicus extracts decreased Bcl-2, Mcl-1, Survivin, and Cyclin D1 mRNA expression and increased Bax mRNA level. O. japonicus extracts also increased Caspase-3 activation. Overall, O. japonicus DW extracts were more effective than EtOH extracts. Conclusions: O. japonicus inhibited cell proliferation and induced apoptosis in SNU-1079 cells via mitochondria -mediated intrinsic pathway, which leads to Caspase-3 activation. The results indicate that O. japonicus is a potential therapeutic herb with anti-tumor effect against intrahepatic cholangiocarcinoma.