• Archives of Pharmacal Research
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• 제29권5호
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• pp.354-362
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• 2006

Dietary flavonoids have attracted a great deal of attention as agents for preventing estrogen-related diseases, such as postmenopausal symptoms, and for reducing the risk of estrogen-dependent cancer. Kaempferol is one of the most commonly found dietary phytoestrogen. The aim of this study was to investigate the estrogenic and/or antiestrogenic effect of kaempferol, which can confirm its potency as a preventive agent against estrogen-related diseases. Kaempferol has both estrogenic and antiestrogenic activity, which are biphasic response on estrogen receptor. The estrogenic activity of kaempferol induced via ER-mediated pathway depending on $E_2$ concentration $(\leq\;10^{-12}M)$. Kaempferol $(10^{-5}\;M)$ also caused antiproliferative effect on MCF-7 cell in the presence of $E_2\;(10^{-11}\;M)$ and restored to the addition of excess $E_2\;(10^{-7}\;M)$, which confirms that antiproliferation of kaempferol was induced via ER-dependent pathway. However, at $10^{-4}\;M$, concentration higher than the concentrations at which the estrogenic effects of kaempferol are detected $(10^{-5}\;M)$, kaempferol induced strong antiproliferative effect, but were unaffected by the addition of excess $E_2\;(10^{-7}\;M)$ indicating that kaempferol exerts antiproliferation via ER-independent pathway. In particular, kaempferol blocked the focus formation induced by $E_2$, which confirms that kaempferol might inhibit the malignant transformation caused by estrogens. Therefore, we suggested that kaempferol might regulate a suitable level of estrogenic activity in the body and is expected to have potential beneficial effects in preventing estrogen imbalance diseases (breast cancer, osteoporosis, cardiovascular disease and etc.).

• Journal of Pharmaceutical Investigation
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• 제38권2호
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• pp.93-98
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• 2008

The drug-eluting stent (DES) implantation is a widely acceptable treatment for coronary heart disease. It was reported that iron chelator had anti-proliferative effect on human vascular smooth muscle cells (HA-VSMCs). In this study, tetraphenylporphine (TPP) was selected as an iron chelator and drug for DES. MTT assay showed that TPP had antiproliferative effect on HA-VSMCs. TPP and polycaprolactone (PCL) were coated onto stainless steel plate using a spraycoating method. From the surface morphology examination of the coated plate by SEM, smooth polymer coating layer could be observed. The thickness of coating layer could be controlled by changing repeating time of coating. From in vitro release test, sustained release of TPP was observed from plate during two weeks. Thus, TPP as iron chelator can be used as drug for stent coating because of its antiproliferative effect and sustain release profile.

• 동의생리병리학회지
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• 제20권4호
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• pp.966-972
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• 2006

The effect of water extract of Chungjogupae-tang (CJGPT) was investigated _on the growth of human lung carcinoma A549 cells. Methods: MTT assay and fluorescent microscope peformed to compare and examine the efficacy of CJGPT treatment on the cytostaticity of lung cancer cells in proportion to time and doses, and DAPI staining and Western blot analysis were used to examine their effect on apoptosis. In addition, the quantitative RT-PCR was used to examine to lung cancer cells growth, and Prostaglandin E2 activity were measured. Results: Exposure of A549 cells to CJGPT respited in the growth inhibition and apoptosis in a dose-dependent manner as measured by MTT assay and fluorescent microscope. The antiproliferative effect by CJGPT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. CJGPT treatment resulted in an up-regulation of cyclin-dependent kinase inhibitor p21 (WAFl/CIPl) in a p53-independent fashion. We found that CJGPT treatment decreased the levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthease (iNOS) expression without significant changes in the expression of COX-1 , which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. Conclusion: These findings suggested that CJGPT-induced inhibition of human lung carcinoma A549 cell growth was connected with the induction of apoptotic cell death and the results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of CJGPT.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.286-292
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• 2008

Strawberry is widely consumed in diet and has been attracted much attention due to its potential for human health benefits. Strawberry contains a diverse range of phytochemicals but the biological activities with molecular mechanisms are poorly elucidated yet. In this study, the effects of the extracts of strawberry (Maehyang cultivar) on antioxidant, antiinflammatory, and antiproliferative potential against various cancer cells were investigated. The strawberry extracts (SE) of Maehyang cultivar showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activities. In addition, SE inhibited the growth of human colon (HCT-116), lung (A549), stomach (SNU-638) and fibrosarcoma (HT-1080) cancer cells. The strawberry extracts also exhibited the inhibitory effect on lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production and suppressed LPS-induced inducible nitric oxide synthase (iNOS) protein and mRNA expression in mouse macrophage RAW 264.7 cells. These findings suggest that the strawberry extracts (Maehyang cultivar) might have antioxidant, antiinflammotry, and anticancer activities.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2305-2309
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• 2012

Crocin, the main pigment of Crocus sativus L., has been shown to have antiproliferative effects on cancer cells, but the involved mechanisms are only poor understood. This study focused on probable effect of crocin on the immortality of hepatic cancer cells. Cytotoxicity of crocin ($IC_{50}$ 3 mg/ml) in hepatocarcinoma HepG2 cells was determined after 48 h by neutral red uptake assay and MTT test. Immortality was investigated through quantification of relative telomerase activity with a quantitative real-time PCR-based telomerase repeat amplification protocol (qTRAP). Telomerase activity in 0.5 ${\mu}g$ protein extract of HepG2 cells treated with 3 mg/ml crocin was reduced to about 51% as compared to untreated control cells. Two mechanisms of inhibition, i.e. interaction of crocin with telomeric quadruplex sequences and down regulation of hTERT expression, were examined using FRET analysis to measure melting temperature of a synthetic telomeric oligonucleotide in the presence of crocin and quantitative real-time RT-PCR, respectively. No significant changes were observed in the $T_m$ telomeric oligonucleotides, while the relative expression level of the catalytic subunit of telomerase (hTERT) gene showed a 60% decrease as compared to untreated control cells. In conclusion, telomerase activity of HepG2 cells decreases after treatment with crocin, which is probably caused by down-regulation of the expression of the catalytic subunit of the enzyme.

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2002년도 제37회 국제학술심포지움 및 추계학술대회
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• pp.36-39
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• 2002

PKB activation may contribute to resistance to antiproliferative signals and breast cancer progression in part by impairing nuclear import and action of p27. PKB transfection caused cytoplasmic p27 accumulation and cytokine resistance. The nuclear localization region of p27 contains a PKB/Akt consensus site at threonine 157 and p27 phosphorylation by PKB impaired its nuclear import in vitro. PKB/Akt phosphorylated wild type p27 but not p27T157A. PKB activation led to cytoplasmic mislocalization of p27WT but p27T157A remained nuclear. In PKB activated cells, p27WT failed to cause Gl arrest, while the antiproliferative effect of p27T157A was not impaired. Cytoplasmic p27 was seen in 41% (52/128) of primary human breast cancers in association with PKB activation. Thus, we show a novel mechanism whereby PKB impairs p27 function that is associated with an aggressive phenotype in human breast cancer.

• Archives of Pharmacal Research
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• 제27권6호
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• pp.640-645
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• 2004

Histone deacetylase inhibitors are new class of chemotherapeutic drugs able to induce tumor cell apoptosis and／or cell cycle arrest. Trichostatin A, an antifungal antibiotic, and HC-toxin are potent and specific inhibitors of histone deacetylase activity. In this study, we have examined the antiproliferative activities of trichostatin A and HC-toxin in estrogen receptor positive human breast cancer, T47D cells. Both trichostatin A and HC-toxin showed potent antiprolifer-ative efficacy and cell cycle arrest at $G_2/M$ in T47D human breast cancer cells in a dose-dependent manner. Trichostatin A caused potent apoptosis of T47D human breast cancer cells and trichostatin A-induced apoptosis might be involved in an increase of caspase-3／7 activity. HC-toxin evoked apoptosis of T47D cells and HC-toxin induced apoptosis might not be medi-ated through direct increase in caspase-3/7 activity. We have identified potent activities of anti-proliferation, apoptosis, and cell cycle arrest of trichostatin A and HC-toxin in estrogen receptor positive human breast cancer cell line T47D.

• 동아시아식생활학회지
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• 제26권3호
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• pp.207-214
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• 2016

This study investigated the effects of ginger (Zingiber officinale Roscoe) on antioxidant and antiproliferative activities in A2058 human melanoma cells. The antioxidant and antiproliferative activities of 70% ethanol extracts of Zingiber officinale Roscoe were identified based on DPPH and ABTS free radical scavenging capacities. Treatment of cells with Zingiber officinale Roscoe at concentrations of 0, 0.2, and 0.4 mg/mL for 24 hours significantly reduced cell viability as determined by Hoechst 33258 nuclear staining, apoptosis analysis, and Western blotting analysis, respectively. In our study, 70% ethanol extracts of Zingiber officinale Roscoe exhibited antioxidant activity and inhibited A2058 cell growth in a dose-dependent manner. Concomitant activation of the mitochondria-dependent apoptotic pathway of A2058 human melanoma cells by Zingiber officinale Roscoe extracts was mediated via modulation of Bax and Bcl-2 expression, which activated cleavage of caspases-3, caspases-9, and poly ADP-ribose polymerase. The findings of study indicate that Zingiber officinale Roscoe extracts induce apoptosis in A2058 human melanoma cells, and this phenomenon occurs via the death receptor-mediated and intrinsic pathways.

• 한국식품영양과학회지
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• 제39권5호
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• pp.731-736
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• 2010

본 연구에서는 재배 방식(비가림과 노지재배)에 따른 대표적인 고추 11개 품종 간의 일부 기능성 성분과 항산화 및 암세포 증식억제 활성의 차이를 알아보고자 하였다. 기능성 성분은 capsaicinoids, polyphenol 및 vitamin C를 분석하였다. 추출물의 항산화력은 ABTS radical 제거능, 환원력, 금속이온 제거능을 이용해 평가하였으며 암세포 증식 억제능은 유방암, 대장암 및 폐암 세포주를 이용하였다. 노지 재배한 11개 품종의 capsaicin, dihydrocapsaicin, polyphenolics 및 vitamin C 함량은 각각 0.0~268.3 mg/100 g, 0~55.1 mg/100 g, 635~878 mg/100 g 및 4.1~8.2 mg/g으로 품종 간 차이를 보였으나 재배방식 간의 유의적인 차이는 보이지 않았다. 기능성 성분 결과와 비슷하게, 품종에 따른 활성의 차이는 있었으나 재배 방식 간 활성에 대한 유의적인 차이는 보이지 않았다. 본 연구 결과는 재배 방식과 고추 품종에 대한 일부 기능성 성분과 활성에 대한 기초자료를 제공하고 있다고 생각한다.

• 한국식품영양과학회지
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• 제37권8호
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• pp.1079-1083
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• 2008

본 연구에서는 고추잎 추출물에 대한 항산화 활성과 암세포 증식억제 활성을 분석하고 각 추출물에 따른 차이를 비교 분석하고자 하였다. 추출물의 항산화력은 ABTS와 DPPH 라디칼 제거능, 환원력 및 금속이온 제거능을 이용하여 평가하였으며 암세포 증식 억제능은 유방암, 대장암 및 위암 세포주를 이용하였다. 각 추출물 중 70% acetone 추출물의 경우 polyphenol 함량(56.6 mg GAE/g residue)과 총 항산화력(450.8 mM TEAC/g residue), DPPH 라디칼 제거능(230.3 mM TEAC/g residue), 환원력(0.5 A700) 측정에서 모두 가장 높은 수치를 나타내었다. 또한 암세포 증식억제활성 측정 결과 대장암세포(HCT116)에서는 70% acetone 추출물이 1 mg/mL의 농도에서 96.2%의 증식억제 활성을 나타냈고 유방암세포(MCF7)에서는 methanol 추출물이 78.4%의 활성을 나타냈으며, 위암세포(MKN45)에서는 water 추출물이 89.7%의 활성을 나타내었다. 본 연구결과는 점차 관심이 높아지고 있는 천연 항산화 항암제로서의 고추잎에 대한 활성연구에 있어 기초자료가 될 것으로 예상되며, 주산물인 고추열매에 비해 그 활용도가 극히 적은 고추잎에 대한 소비촉진에 영향을 끼칠 것으로 기대된다.