• Journal of Korean Neurosurgical Society
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• 제42권5호
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• pp.392-399
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• 2007

Objective : Arsenic trioxide ($As_2O_3$) has been used as an anticancer agent in traditional Chinese medicine for thousand years and berberine is an isoquinoline alkaloid present that has indicated significant antimicrobial activity. We have examined the combined anticancer effects of $As_2O_3$ and berberine against the human neuroblastoma (HNB) SH-SY5Y cells in vitro, and to elucidate underlying molecular mechanism. Methods : HNB SH-SY5Y cells were treated with $2\;{\mu}M\;As_2O_3$ and $75\;{\mu}g/ml$ berberine, and their survival, cell death mechanism as well as synergistic cytotoxic effects were estimated by using MTT assay, DAPI staining, agarose gel electrophoresis, flow cytometric analysis, and western blot analysis. Results : The combined treatment of two drugs also markedly decreased cell viability. The cytotoxic effects of two drugs were revealed as apoptosis characterized by chromatin condensation, DNA fragmentation, and the loss of mitochondrial membrane potential. The apoptotic cytotoxicity was accompanied by activation of caspase-3 protease as well as decreased the expression of Bcl-2, Bid, and Bcl-x/L. In addition, the cells treated with combination of two drugs also showed significantly increased intracellular reactive oxygen species levels and lipid peroxidation compared to cells $As_2O_3$or berberine only. Conclusion : Combined treatment of $As_2O_3$ with berberine induced activation of apoptotic signaling pathways in HNB SH-SY5Y cells. These results suggest that the possibility of the combined treatment of two chemotherapeutic agents with low concentration improving cytotoxic effect for cancer cells with minimal side effects.

• Parasites, Hosts and Diseases
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• 제53권1호
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• pp.21-27
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• 2015

Plants used for traditional medicine contain a wide range of substances that can be used to treat various diseases such as infectious diseases. The present study was designed to evaluate the antileishmanial effects of the essential oil and methanolic extract of Myrtus communis against Leishmania tropica on an in vitro model. Antileishmanial effects of essential oil and methanolic extract of M. communis on promastigote forms and their cytotoxic activities against J774 cells were evaluated using MTT assay for 72 hr. In addition, their leishmanicidal activity against amastigote forms was determined in a macrophage model, for 72 hr. Findings showed that the main components of essential oil were ${\alpha}$-pinene (24.7%), 1,8-cineole (19.6%), and linalool (12.6%). Findings demonstrated that M. communis, particularly its essential oil, significantly (P<0.05) inhibited the growth rate of promastigote and amastigote forms of L. tropica based on a dose-dependent response. The $IC_{50}$ values for essential oil and methanolic extract was 8.4 and $28.9{\mu}g/ml$ against promastigotes, respectively. These values were 11.6 and $40.8{\mu}g/ml$ against amastigote forms, respectively. Glucantime as control drug also revealed $IC_{50}$ values of 88.3 and $44.6{\mu}g/ml$ for promastigotes and amastigotes of L. tropica, respectively. The in vitro assay demonstrated no significant cytotoxicity in J774 cells. However, essential oil indicated a more cytotoxic effect as compared with the methanolic extract of M. communis. The findings of the present study demonstrated that M. communis might be a natural source for production of a new leishmanicidal agent.

• Natural Product Sciences
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• 제26권1호
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• pp.59-63
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• 2020

This study focused on investigation of the immunosuppressive inhibitory effect through determination of IL-2 production of nine compounds (1 - 9) isolated from Chlamydomonas sp. KSF108. Among them, compounds 1, 5, and 6 displayed moderately inhibitory effects on IL-2 production at a concentration of 100 µM. In addition, the related ones including cytotoxic, anti-inflammatory, and anti-oxidant activities were also elucidated. 6 further displayed cytotoxic activity against the MCF-7 cell line, with an IC₅₀ value of 17.2 µM and 4, 6 - 7, and 9 possessed significant DPPH radical scavenging activity, with IC₅₀ values ranging from 3.1 to 4.4 µM. To the best of our knowledge, this is the first report on the bioactivity of isolated chemical constituents from the genus Chlamydomonas. Compounds 1 and 5 investigated for the first time in the activity of immunosuppressivity and 6 may come to serve as the most important marker in broad-spectrum activities of the secondary metabolites identified from C. sp. KSF108.

• 동의생리병리학회지
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• 제19권3호
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• pp.802-810
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• 2005

The tetrahydroisoquinolines included potent cytotoxic agents that showed antitumor activity,antimicrobial activity, and other biological properties. We studied the effect of CDST, 1-Chloromethyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-sulfonic acid amide, a newly synthesized anti-cancer agent. The cytotoxic activity of CDST in HL-60 cells was increased in a dose-dependent manner. CDST, tetrahydroisoquinolines derivative, was cytotoxic to HL-60 cells, with IC50 of $80{\mu}g/ml$. Treatment of CDST to HL-60 cells showed the fragmentation of DNA in a dose- and time dependent manner, suggesting that thesecells underwent apoptosis. Treatment of HL-60 cells with CDST was induced in a dose- and time-dependent activation of caspase-3, caspase-8 and proteolytic cleavage of poly(ADP-ribose) polymerase. In caspase activity assay, caspase-3 and -8 was activated after 12 h and 6 h posttreatment, respectively. CDST also caused the release of cytochrome c from mitochondria into the cytosol. CDST-induced cytochrome c release was mediated by caspase-8-dependent cleavage of Bid and Bax translocation. These results suggest that caspase-8 induced Bid cleavage and Bax translocation, caused mitochondrial cytochrome c release, and induce caspase-3 activationduring CDST-induced apoptosis in HL-60 cells.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.74-74
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• 1993

The in vitro cytotoxicity of SKI 2053R was evaluated against human tumor cell lines along with those of cisplatin and carboplatin using MTT assay. The cell lines tested were two human lung cancer cell lines and five human stomach cancer celt lines. The level of cytotoxic effects of SKI 2053R against two human lung cancer cell lines was located between cisplatin and carboplatin. However, the cytotoxic activity of SKI 2053R against five human stomach cancer cell lines was similar to that of cisplatin. SKI 2053R is considered to be selectively cytotoxic toward human stomach cancer cell lines. We carried out pharmacokinetic and ex vivo phrmacodynamic studies of SKI 2053R in beagle dogs to predict the clinical antitumor effect of SKI2053R, comparing with those of cisplatin and carboplatin. In ex vivo pharmacodynamics which used MTT assay as bioassay on the 2 lung and 5 stomach cancer cell, mean antitumor indexes (ATIs) of SKI 2053R were highest among three compounds in both lung and stomach cancer cell lines, especially in stomach cancer cell. Much higher ATI profile and maximal inhibition rates of SKI 2053R appeared in the stomach cancer cells will give desirable advantages to clinical trial s against gastric carcinoma. The anti tumor activity and target organ toxicity of SKI 2053R were compared with those of cisplatin on stomach cancer cell line, KATO III xenografted into nude BALB/c(nu/nu) mice. All groups of cisplatin and SKI 2053R showed active tumor regression. The inhibition rates(IR) of SKI 2053R were higher than that of cisplatin on the basis of mean IR. Though the loss of body weight was observed in all groups from the first week, the SKI 2053R group recovered it soon from the third week after the initiation of treatment, maintaining the most active anti tumor activity among three groups.

• 한국자원식물학회지
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• 제10권4호
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• pp.411-417
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• 1997

더덕의 재배기술 개선을 목적으로 Uniconazol 및 Paclobutrazol을 더덕의 생장기별로 엽면산포(葉面散布)를 행했다. Uniconazol 및 Paclobutrazol 처리는 처리시기에 관계 없이 농도가 높을수록 초장은 억제되었으며 엽면적(葉面積)의 감소를 나타냈다. Uniconazol 처리에 의한 지하부의 형질은 3절(節) 분화시의 처리를 제외한 모든 처리구에서 대조구와의 유의차가 인정되지 않았다. 그러나12절 분화시의 10mg $liter^1$ 와 100mg $liter^1$ 농도처리에서는 대조구보다 생체중(生體重)이 각각 64%, 100%의 증가를 보였다. 세포독성(細胞毒性) Screening의 결과는 대조구 및 6절 분화시 10mg $liter^1$ 처리구에서만 활성을 나타했다. Paclobutrazol 처리에 의한 지하부의 생체중(生體重)은 3절(節) 분화시의 처리를 제외한 모든 처리구에서 대조구와의 유의차가 인정되지 않았다. 그러나 12절 분화시의 10mg $liter^1$ 농도처리에 의해 조금의 증가를 보였다. 세포독성(細胞毒性) Screening의 결과는 대조구 및 모든 처리구에서 약한 활성치를 나타냈다.

• Biomolecules & Therapeutics
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• 제30권5호
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• pp.465-472
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• 2022

Melanoma is one of the most aggressive skin cancers. Hypoxia contributes to the aggressiveness of melanoma by promoting cancer growth and metastasis. Upregulation of cyclin D1 can promote uncontrolled cell proliferation in melanoma, whereas stimulation of cytotoxic T cell activity can inhibit it. Epithelial mesenchymal transition (EMT) plays a critical role in melanoma metastasis. Hypoxia-inducible factor-1α (HIF-1α) is a main transcriptional mediator that regulates many genes related to hypoxia. CoCl₂ is one of the most commonly used hypoxia-mimetic chemicals in cell culture. In this study, inhibitory effects of IDF-11774, an inhibitor of HIF-1α, on melanoma growth and metastasis were examined using cultured B16F10 mouse melanoma cells and nude mice transplanted with B16F10 melanoma cells in the presence or absence of CoCl₂-induced hypoxia. IDF-11774 reduced HIF-1α upregulation and cell survival, but increased cytotoxicity of cultured melanoma cells under CoCl₂-induced hypoxia. IDF-11774 also reduced tumor size and local invasion of B16F10 melanoma in nude mice along with HIF-1α downregulation. Expression levels of cyclin D1 in melanoma were increased by CoCl₂ but decreased by IDF-11774. Apoptosis of melanoma cells and infiltration of cytotoxic T cells were increased in melanoma after treatment with IDF-11774. EMT was stimulated by CoCl₂, but restored by IDF11774. Overall, IDF-11774 inhibited the growth and metastasis of B16F10 melanoma via HIF-1α downregulation. The growth of B16F10 melanoma was inhibited by cyclin D1 downregulation and cytotoxic T cell stimulation. Metastasis of B16F10 melanoma was inhibited by EMT suppression.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2022년도 추계학술대회
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• pp.95-95
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• 2022

Kadsura heteroclita (Roxb.) Craib and Eichhornia crassipes (Mart.) Solms. have been known to give effects on pimple. Jatropha gossypiifolia L., Anisomeles indica (L.) Kuntze, Kadsura heteroclita (Roxb.) Craib extracts have been used for cough cold for a long time. To test whether Jatropha, Anisomeles, Kadsura and Eichhornia have anti-oxidant acitivity, we performed DPPH assay. Jatropha showed 91.98% anti-oxidant activity and Anisomeles, Eichhornia and Kasuda showed 47.91%, 47.35% and 32.00% anti-oxidant activity, respectively, compared to Ascorbic acid control. To further determine whether these extracts have any cytotoxic effects, we used MTT assay with these extracts in Raw264.7 cells. Jatropha showed 45.10% survival rate and Anisomeles, Eichhornia and Kasuda showed 76.78%, 86.24% and 82.88% survival rate, respectively, compared to negative control. Taken together, these results suggest that Jatropha showed higher anti-oxidant activity than other plant extracts, however it has cytotoxic effect. Therefore, we consider Anisomeles, Eichhornia and Kasuda extracts might be a good candidate to develop as a therapeutic agent with higher anti-oxidant acitivity and lower cytotoxic effects among the tested plant extracts.

• 동의생리병리학회지
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• 제16권6호
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• pp.1197-1200
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• 2002

To examine the cardiotoxicity of glucose oxidase(GO) in cultured myocardial cells, cardiotoxicity was measured by MTT assay. Myocardial cells were treated with 1～50 mU/ml GO for 5 hours. The cardioprotective effect of Benincasae Semen(BS) was measured by MTT assay in these cultrures. Cell viability was significantly decreased in dose- and time-dependently after myocardial cells were exposed to 30mU/ml GO for 5 hours. In the cardioprotective effect of BS on the cardiotoxicity induced by GO, BS prevented the cardiotoxicity induced by GO in these cultures. From these results, it suggests that GO had cytotoxic effect in cultured myocardial cells and herb extract, BS showed protective effect on GO-induced cardiotoxicity.

• 동의생리병리학회지
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• 제17권5호
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• pp.1231-1234
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• 2003

To clerify the toxic effect of methylmercuric chloride(MMC) in cultured mouse myocardial cells, cytotoxic effect was measured by MTT assay after cultured myocardial cells were incubated for 48 hours in the media containing 1～30 uM concentrations of MMC. And also, the protective effect of Benincasae Semen (BS) was assessed in these cultrures. Cell viability was significantly decreased in a dose-dependent manner after cultured myocardial cells were exposed to 30 uM MMC for 48 hours. In the neuroprotective effect of BS on MMC-induced cytotoxicity, BS blocked the MMC-induced myotoxicity in these cultures. From these results, it suggests that MMC is toxic on cultured mouse myocardial cells and BS is effective in blocking the neurotoxicity induced by MMC.