• 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.157.3-158
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• 2003

The antioxidant and anticancer properties of a medicinal plant, Betula platyphylla var. japonica were investigated. The total methanol extract of B. platyphylla var. japonica had protective effects against hydrogen peroxide ($H_2O_2$) in the Chinese hamster lung fibroblast (V79-4) cell line and induced apoptotic cell death in human promyelocytic leukemia (HL-60) cells, a cancer cell line. B. platyphylla var. japonica extract significantly increased cell viability against $H_2O_2$. The extract also showed high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity ($IC_50$ 2.4 mg/ml) and lipid peroxidation inhibitory activity ($IC_50$ below 4.0 mg/ml). (omitted)

• 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.199.1-199.1
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• 2003

In the course of our search for intercellular adhesion molecule-1 (ICAM-1)/leukocyte function-associated antigen-1 (LFA-1) mediated cell adhesion inhibitors from natural sources, new type of cell adhesion inhibitors were isolated from the MeOH extract of Saururus chinensis roots. On the basis of spectral evidence, the structures of the active compounds were identified as manassantin A and B. Manassantin A and B inhibited phorbol 12-myristate 13-acetate (PMA)-induced homotypic aggregation of the human promyelocytic leukemia HL-60 cells without cytotoxicity with MIC value of 1.0 and 5.5 nM, respectively. (omitted)

• 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.338.2-338.2
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• 2002

Ceramide is a lipid second messenger that is involved in apoptotic cell death. In this study, we show that p38 MAPK plays an important role in the regulation of ceramide-induced apoptosis. We found that SB203580, a p38 kinase inhibitor, blocked the effects of ceramide to induce Bax translocation to mitochondria, activation of caspase-3, and DNA fragmentation. Furthermore. expression of a dominant negative form of p38 MAPK suppressed ceramide-induced Bax translocation, suggesting that p38 kinase activity is essential for Bax translocation. (omitted)

• 대한한방피부미용학회지
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• 제1권1호
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• pp.127-144
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• 2005

This study compared the activity of the aerial part of P. japonicum with its root in order to examine the possibility of the medicinal use of the aerial part, which has not been used as medicine, in substitute for the root that has traditionally been used as medicine. For this purpose, the author measured the proliferation of Human $CD4^-$ T cells, which are related to immunity, the differentiation of HL-60 cells, and the contents of IL-6, IgE and $TNF-{\alpha}$ and compared their anti-cancer effect on Hep3B and A549 cells. The results of this study are as follows: 1. As for Human $CD4^-$ T cells, $1.0\;g/{\ell}$ methanol extract from the aerial part promoted the proliferation of the cells 1.8 times higher while $1.0\;g/{\ell}$ methanol extract from the root did by 1.76 times higher compared to the control group. 2. As for HL-60 cells, methanol extract and water extract from the aerial part showed differentiation 1.14 times higher and 1.12 times higher respectively while methanol extract and water extract from the root did 1.14 times higher and 1.07 times higher compared to tile control group. 3. Cell density was highest on Day 4 of culture in all samples, Methanol extracts from the aerial part and the root showed activities of $7.9{\times}10^3\;cells/m{\ell}$ and $7.5{\times}10^3\;cells/m{\ell}$ respectively, and water extracts from the aerial part and the root did activities of $5.3{\times}10^3\;cells/m{\ell}$ and $6.1{\times}10^3\;cells/m{\ell}$. 4. The secretion of IL-6 was highest on Day 4 of culture. Methanol extracts from the aerial part and the root showed secretions of $6.7{\times}10^{-3}\;pg/cells/m{\ell}$ and $7.2{\times}10^{-3}\;pg/cells/m{\ell}$ respectively, and water extracts from the aerial part and the root did secretions of as high as $7.0{\times}10^{-3}\;pg/cells/m{\ell}$ and $6.0{\times}10^{-3}\;pg/cells/m{\ell}$. 5. As for the production of IgE, water extract from the root effectively inhibited the product at $1,000\;{\mu}g/m{\ell}$, methanol extract from the root at $10\;{\mu}g/m{\ell}$ and $100\;{\mu}g/m{\ell}$, water extract from the aerial at $1,000\;{\mu}g/m{\ell}$, and methanol extract from the aerial part at $1,000\;{\mu}g/m{\ell}$. 6. According to the result of measuring the content of $TNF-{\alpha}$, methanol extracts from the root and the aerial part showed inhibition effect at $10\;{\mu}g/m{\ell}$, $100\;{\mu}g/m{\ell}$ and $1,000\;{\mu}g/m{\ell}$. 7. As for liver cancer cell Hep3B, $1.0\;g/{\ell}$ methanol extracts from the root and the aerial part showed inhibition effects of 78% and 70% respectively, and $1.0\;g/{\ell}$ water extracts from the root and the aerial part did inhibition effects of 56% and 59%. 8. As for lung cancer cell A549, $1.0\;g/{\ell}$ methanol extracts from the root and the aerial part showed inhibition effects of 75% and 70% respectively, and $1.0\;g/{\ell}$ water extracts from the root and the aerial part did inhibition effects of 48% and 45%. The results of this study presented above show that the aerial part of P. japonicum has immunizing and anti-cancer effects as high as its root, which has commonly been used as medicine. There should be more in-depth research on the aerial part of P. japonicum in the future.

• 한국미생물·생명공학회지
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• 제34권2호
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• pp.143-149
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• 2006

담수 혹은 해수에서 배양한 S. platensis의 추출조건에 따른 수율을 비교하기 위해 60$^{\circ}C$와 100$^{\circ}C$에서 물과 에탄올을 이용하여 추출하여 추출 수율을 비교한 결과 해수 S. platensis가 약 3% 정도 높은 추출 수율을 나타내었다. 그리고 각 추출물의 정상세포에 대한 세포 독성을 살펴보기 위하여 인간 정상 신장 세포(HEK293)를 이용하였으며, 모든 시료에서 1.0 mg/ml의 농도에서 26%이하의 비교적 낮은세포독성을 나타내었고, 그 중 해수 S. piatensis가 담수 S. piatensis보다 약 5% 정도 낮은 세포독성을 나타내었다. 그리고 암세포에 대한 암세포 생육 억제 활성을 측정한 결과 4가지 암세포 주인 폐암세포(A459)와 위암세포(AGS), 유방암세포(MCF-7)와 간암세포(Hep3B)에 대해 모든 추출물에 대해 1.0 mg/ml의 농도에서 70%이상의 높은 암세포 생육억제 효과를 나타내었고, 그 중 해수 S. platensis의 60$^{\circ}C$물 추출물에서 80%이상으로 가장 높은 암세포 생육 억제 효과를 나타내었다. 선택적 사멸도는 모든 암세포에서 1.5 이상으로 나타나 암세포에 대해 선택적으로 사멸시키는 것으로 나타났다. 담수 혹은 해수를 사용하여 배양한 경우 해수 S. platensis가 추출 수율뿐만 아니라 정상세포에 대한 세포독성 및 암세포 생육 억제 활성에서 높은 효과를 나타내었다. 인간 전골수세포인 HL-60세포를 이용한 세포분화도를 측정한 결과 60$^{\circ}C$에서 물을 이용하여 추출한 해수 S. platensis에서 담수 S. platensis보다 5일째 약 20% 정도의 높은 세포 분화 활성을 나타내었다.

• Journal of Microbiology and Biotechnology
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• 제11권5호
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• pp.749-755
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• 2001

High Electromagnetic Field (EMF) with an intensity of 1 mT (Tesla) inhibited the growth of both human normal lung and immune T cell down to $20-30\%$, compared to that of an unexposed case. The human T-cells, Jurkat, were more severely affected by EMF than the human lung cells, which showed a relatively slow cell growth and substantial releas of $Ca^+2$ (3.5 times higher than the human T-cells). However, the growth of hepatoma carcinoma, Hep3B, was enhanced by twice that of an unexposed case. The EMF intensity and exposure time did not affect the growth of the cancer cells very much, while it significantly affected the growth of normal cells. Accordingly, it is possible that EMFs may play a role in the initiation of cancer. The EMFs disturbed the signal transduction and membrane systems, such that a five times higher amount of PKC-${\alpha}$ was released from the cell membrane than in the control. Extended exposure to EMFs, for more than 48 hours, also led to 1 $90\%$ necrotic death pattern from apoptotic cell death. Finally, EMF at an intensity of 1mT with a 24-T exposure promoted the differentiation of HL-60 cells to monocytes/macrophages, possibly causing potential acute leukemia.

• BMB Reports
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• 제48권2호
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• pp.109-114
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• 2015

The COX-2/$PGE_2$ pathway has been implicated in the occurrence and progression of cancer. The underlying mechanisms facilitating the production of COX-2 and its mediator, $PGE_2$, in cancer survival remain unknown. Herein, we investigated $PGE_2$-induced COX-2 expression and signaling in HL-60 cells following menadione treatment. Treatment with $PGE_2$ activated anti-apoptotic proteins such as Bcl-2 and Bcl-xL while reducing pro-apoptotic proteins, thereby enhancing cell survival. $PGE_2$ not only induced COX-2 expression, but also prevented casapse-3, PARP, and lamin B cleavage. Silencing and inhibition of COX-2 with siRNA transfection or treatment with indomethacin led to a pronounced reduction of the extracellular levels of $PGE_2$, and restored the menadione- induced cell death. In addition, pretreatment of cells with the MEK inhibitor PD98059 and the PKA inhibitor H89 abrogated the $PGE_2$-induced expression of COX-2, suggesting involvement of the MAPK and PKA pathways. These results demonstrate that $PGE_2$ signaling acts in an autocrine manner, and specific inhibition of $PGE_2$ will provide a novel approach for the treatment of leukemia.

• 한국약용작물학회지
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• 제13권4호
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• pp.161-170
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• 2005

당귀, 복분자, 마황의 추출공정 요인별 [추출온도 $(40^{\circ}C,\;60^{\circ}C,\;100^{\circ}C)$, 초음파 병행 (처리조건 : 초음파별) 추출]에 따른 추출물들의 분획물들의 추출수율 증진 및 생산성 향상이 가능한 공정 개발을 위하적 공정 요인에 따라 추출과 분획을 실시하였다. 그 중 모든 분획 추출물 들 중에서 $60^{\circ}C$ 온도에서 40kHz의 초음파 병행 추출한 복분자 water 분획층 수율이 59.63%로 다른 추출 공정에 비하여 가장 높게 나타났으며, 당귀 water 분획층의 수율은 50.17%로 나타나 water 분획층의 수율이 가장 높게 나타났으며, butanol, ethyl acetate, chloroform 분획층의 순서로 수율이 나타난 것을 확인 할 수 있었다. 이것으로 $60^{\circ}C$의 40 kHz 초음파 병행 추출 공정이 생산성이 가장 우수한 것으로 나타났다. 면역활성 증진 효과에서 인간의 면역세포인 B, T 세포에 대한 생육 활성도를 각 공정별 추출물을 이용하여 측정한 결과 $60^{\circ}C$의 40 kHz의 초음파 병행 추출물의 water 분획물에서 180% 이상의 높은 생육 활성도를 나타내었고, butanol 분획물에서는 160% 이상의 높은 생육 활성도를 나타내었다. Cytokines 분비량은 면역 세포에 대한 활성 실험에서 효과가 가장 높게 나타났던 추출공정인 $60^{\circ}C$의 40 kHz 초음파 병행 추출물의 water 분획층과 butanol 분획층을 이용하여 분획물 실험을 행하였다. B세포에서의 IL-6 분비량에 복분자 water 분획충이 1.0 g/l에서 5일째 $17{\times}10^{-4}\;ph/cell$로 가장 높은 증진 효과를 나타내었으며, butanol 분획층이 $16.8{\times}10^{-4}\;pg/cell$의 증진효과를 보였고, 마황과 당귀 water 분획층이 각각 $16.5{\times}10^{-4}\;pg/cell,\;16.5{\times}10^{-4}\;pg/cell$의 증진효과를 보였다 B 세포에서의 $TNF-{\alpha}$분비량은 복분자 water 분획층이 1.0 g/l에서 5일째 $18{\times}10^{-4}\;pg/cell$로 가장 증진 효과가 크게 나타났다. 이것은 세포의 생육이 시간에 따라 증가됨으로서 그에 따른 cytokines의 분비량도 시간에 따라 증가하는 것으로 사료된다. 추출공정 요인인 온도와, 초음파를 달리하여 그것의 분획물인 water 분획층과 butanol 분획층에 대한 T 세포에서의 cytokine 분비량을 측정한 결과 온도의 변화를 준 추출공정에서의 IL-6분비량은 $60^{\circ}C$에서 가장 좋은 분비량을 나타낸 것으로 복분자가 $18.5{\times}10^{-4}\;pg/cell$로 가장 높은 증진 효과를 나타내었다. 마황과 당귀 또한 $60^{\circ}C$로 추출하였을 때, 1.08배, 1.04배 높은 분비량을 나타내었다. 또한 초음파의 주파수의 변화를 주어 추출한 것으로 T세포의 $TNF-{\alpha}$ 분비량을 측정한 결과 40 kHz의 초음파 병행 추출한 복분자 water 분획층이 1.0 g/l 농도에서 $20.4{\times}10^{-4}\;pg/cell$로 60 kHz로 병행 추출한 복분자 water 분획층의 $19.5{\times}10^{-4}\;pg/cell$보다 높은 분비량을 나타내었다. 당귀와 마황에서도 40 kHz의 초음파로 병행 추출한 것이 더 높은 분비량을 나타내었다. NK-cell의 활성도를 공정 요인별로 측정한 결과 가장 좋은 활성도를 나타낸 것으로는 $60^{\circ}C$에서 40 kHz의 초음파로 병행 추출한 복분자 water 분획층 이 배양 6일째 날 1.0 g/l의 농도에서 97%, butanol 분획층은 93%의 활성증진을 보여 초음파 병행 추출하지 많은 것과 다른 온도 조건에 비해 높은 생육 활성도를 나타내었다. 그리고 당귀 분획물 또한 $60^{\circ}C$, 40 kHz의 초음파 추출물의 water 분획층과 butanol 분획층에서 각 92%와 80%의 활성 증진을 나타내 다른 추출 공정보다 높은 활성을 나타내었다. 이것으로 알 수 있듯이 생체 방어 기능을 증진 시킬 수 있는 최적의 추출공정으로는 $60^{\circ}C$에서 40 kHz의 초음파를 병행하여 추출하는 것으로 사료된다. 세포 분화활성도의 측정 결과는 복분자 water분획층이 가장 높은 세포 분화 활성도를 나타내었고, 또한 복분자와 마황의 분획물이 crude 상태의 초음파 병행 추출물에 비해 최고 20% 이상의 분화 활성도를 나타내는 것을 확인 할 수 있었다.

• Journal of Microbiology and Biotechnology
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• 제10권1호
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• pp.16-20
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• 2000

The aqueous extract from the cultural mycelium of Paecilomyces japonica showed cytotoxicity against several tumor cells including Jurkat, U937, HL-60, HepG2, BW5147.G.1.4, and NIH3T3. When the aqueous extract was fractionated by sequential organic solvent extractions using n-hexane and ethyl acetate, the ethyl acetate fraction appeared to contain the most cytotoxic activity, and the $IC_{50}$ values for various tumor cells were in the range from 1.5 to $10.0{\;}\mu\textrm{g}/ml$. To elucidate the cellular mechanism underlying the induced cytotoxicity, the apoptotic DNA fragmentation along with the cell cycle proression was examined in Jurkat T cells following the ethyl acetate fraction treatment. In the presence of $2.5{\;}\mu\textrm{g}/ml$ of the ethyl acetate fraction, apoptotic DNA fragmentation of the cells was detected within 1 h and increased upto 24 h in a time-dependent manner. Under the same conditions, a sub-G1 peak was detectable by flow cytometry. These results indicate that the cytotoxic effect of P. japonica on tumor cells is attributable to the induced apoptosis.

• 동의생리병리학회지
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• 제16권6호
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• pp.1143-1150
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• 2002

Recent evidence suggests that many Oriental Medicinal prescriptions are effective in cancer patients as a supportive care. Oriental Medicinal herbs have been investigated extensively and are known to have multiple pharmacological effect. These herbs contain a variety of ingredients which may act synergistically to inhibit tumor cell division, to increase tumor cell death (apoptosis), and to increase the proportion of immune cells within tumor. Paljinhangahm-dan (Paljin) has been used to treat for cancer patients in Oriental Medicine for decades. The effects of aqueous extract of Paljin on the induction of apoptotic cell death were investigated in human leukemia cell lines (HL-60, Jurkat, Molt-4 and U937). The viability of leukemia cells was markedly decreased by Paljin in a dose-dependent manner. Paljin induced the apoptotic death of leukemia cells, which was characterized by the ladder-pattern DNA fragmentation, and chromatin condensation of the nuclei. Paljin digested Bid protein but did not affect Bcl-2 protein level and also, induced mitochondrial dysfunction disrupted as shown as the mitochondrial membrane potential. It activated caspase-9 and caspase-3. thereby resulted in cleavage of poly(ADP) ribose polymerase(PARP). These results indicate that Paljin induces apoptosis of human leukemia cells via activation of intrinsic caspase cascades with mitochondrial dysfunction.