• 한국식품영양과학회지
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• 제38권4호
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• pp.442-450
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• 2009

후추의 주요 성분인 piperine은 다양한 생리활성을 나타내고 있으며, 특히 암예방 효과가 있는 것으로 생각되고 있다. 본 연구에서는 piperine의 항암 효과를 밝히기 위해 piperine이 인간의 대장에서 유래한 암세포인 HT-29 세포의 증식에 미치는 영향과 작용 기전을 연구하였다. Piperine을 HT-29 세포 배양액에 여러 농도($0{\sim}40{\mu}M$)로 첨가하여 세포를 배양한 경우 piperine 처리 농도가 증가할수록 세포의 증식이 감소하였고, 세포사멸이 증가하였다. 이는 piperine이 HT-29 세포의 세포사멸을 유도하여 세포 증식을 억제함을 제시한다. Piperine의 세포사멸 기전을 조사하기 위해 세포사멸 조절인자의 변화를 조사하였다. Piperine에 의해 anti-apoptotic Bcl-2 family 단백질인 Bcl-2와 Mcl-1 단백질 수준은 감소하였고, BH3-only 단백질인 Bid 단백질 수준은 감소하였으나, Bik 단백질 수준은 증가하였다. 또한 piperine에 의해 미토콘드리아 막의 투과성이 증가하였고, cytochrome c의 세포질로의 방출이 증가하였다. 또한 piperine 처리에 의해 caspase의 활성형인 cleaved caspase-8, -9, -7, -3 단백질 수준이 증가하였고, PARP의 불활성형인 cleaved PARP 수준이 증가하였다. Caspase의 활성을 저해하는 세포사멸억제단백질 중의 하나인 survivin 단백질 발현이 piperine에 의해 감소하였다. 이 결과로부터 대장암세포인 HT-29 세포에서 piperine이 Bcl-2 family 단백질 발현 변화를 초래하여 미토콘드리아 막 투과성 증가시키고 cytochrome c 방출을 증가시키고, caspase 활성을 증가시키고 survivin 단백질 발현을 억제하여 세포사멸을 유도하여 항암 효과를 나타냄을 알 수 있다. 본 연구는 piperine이 대장암에 강한 항암 효과가 있음을 밝혔으나 향후 암예방 및 암치료제로서 piperine을 활용하기 위해서는 동물실험 및 임상실험 등 다양한 추가 실험이 필요할 것으로 보인다.

• Toxicological Research
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• 제25권4호
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• pp.181-188
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• 2009

Uncontrolled cell growth and increased cell proliferation are major features of cancer that are dependent on the stable structure and dynamics of the cytoskeleton. Since stable cytoskeleton structure and dynamics are partly regulated by myosin light chain kinase (MLCK), many current studies focused on MLCK inhibition as a chemotherapeutic target. As a potent and selective MLCK inhibitor, ML-7 [1-(5-iodonaphthalene-1-sulfonyl)-1 H-hexahydro-1,4-diazapine hydrochloride] is a promising candidate for an anticancer agent, which would induce apoptosis as well as prevents invasion and metastasis in certain types of cancer cells. This study assessed cytotoxic effects of ML-7 against HL-60 cells and therapeutic efficacy of ML-7 as a potential antileukemia agent. Trypan-blue exclusion assays showed dose- and time- dependent decreases in ML-7 treated HL-60 cells (p<0.05). Comet assays revealed a significant increase in DNA damage in HL-60 cells after treatment with $40{\mu}M$ ML-7 for 2h. Sub-G1 fractions, analyzed by flow cytometry increased in a dose-dependent manner, suggesting that ML-7 can induce apoptotic cell death in HL-60 cells. ML-7 was selectively cytotoxic towards HL-60 cells; not affecting normal human lymphocytes. That selective effect makes it a promising potential anti-leukemia agent. In addition, anticancer efficacy of ML-7 in combination with flavonoids (genistein or quercetin) or anticancer drugs (cisplatin or Ara-C) against HL-60 cells was assessed. Combination of ML-7 with flavonoids increased the anti-cancer effect of ML-7 to a greater extent than combination with the anticancer drugs. This implies that ML-7 in combination with flavonoids could increase the efficacy of anticancer treatment, while avoiding side effects cansed by conventional anticancer drug-containing combination chemotherapy.

• 생명과학회지
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• 제34권5호
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• pp.287-295
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• 2024

간세포암종은 전 세계적으로 암 관련 사망의 두 번째 주요 원인으로 새로운 치료 전략을 필요로 한다. 간세포암종 환자를 치료에 사용되는 화학요법제는 독성이 있고 심각한 부작용이 있는 것으로 알려졌다. 본 연구는 건강한 간세포에서 세포독성을 일으키지 않으면서 종양세포를 표적으로 하는 부작용을 감소시키는 항암제의 효능을 조사하였다. Berberine은 이소퀴놀린 알칼로이드의 식물 유래 화합물로 다양한 약리학적 특성으로 인해 암 치료의 잠재적 후보군으로 보고되고 있다. 간암 세포 생존율에 대한 berberine의 효과는 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide 분석을 사용하여 측정하였다. HCC 증식은 콜로니 형성 분석을 통해 실시하였다. 세포이동에 대한 berberine의 효과는 상처 치유 분석으로 실시하였다. Berberine은 HepG2 세포와 같은 간암 세포의 증식과 콜로니 형성 및 세포이동을 억제하였다. Berberine 처리는 Beclin-1 및 LC3-II 등의 자가포식 관련 유전자 발현과 단백질 발현을 증가시켰으며, Caspase-3 및 Caspase-9등의 세포자멸사의 mRNA 발현 및 활성을 증가시켰다. 또한, 세포유래 이종이식 동물실험에서 berberine 처리에 따른 종양의 크기와 무게가 감소함을 확인하였다. 본 연구 결과는 간세포암에 대한 베르베린의 효능을 조명하여 표적 및 맞춤형 치료의 기회를 제시할 수 있음을 시사한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4651-4657
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• 2014

The development of chemopreventive approaches using a concoction of phytochemicals is potentially viable for combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferative effects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil) against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growth of HCT 116 cells more potently ($IC_{50}$ of 3mg/mL) in comparison to Gelam honey ($IC_{50}$ of 75mg/mL). Combined treatment of the two compounds (3mg/mL ginger+75mg/mL Gelam honey) synergistically lowered the $IC_{50}$ of Gelam honey to 22mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibiting effects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggested that individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition, treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dose-dependently while treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes. Combination index analysis showed the combination effect of both natural compounds to be synergistic in their inhibitory action against HCT 116 colon cancer cells (CI 0.96 < 1). In conclusion, combined treatment of Gelam honey and ginger extract could potentially enhance the chemotherapeutic effect of 5-FU against colorectal cancer.

• 구강회복응용과학지
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• 제31권4호
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• pp.340-348
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• 2015

임플란트주위염(peri-implantitis)은 기능중인 골유착 임플란트 주위의 조직에서 생기는 사이트 별 감염성 질환이며 임플란트 후기 실패(late failure)의 원인으로 가장 높은 비율을 차지한다. 여러 연구들을 통해 미생물 침착이 임플란트주위염에 미치는 영향이 보고된 바 있으며 세균막의 제거는 임플란트주위염의 치료 시 필수조건이 된다. 최근에 여러 연구들을 통해 티타늄 임플란트에 레이저를 사용하여 표면을 살균, 정화 시키는 방법에 대한 실험이 많이 보고되고 있다. 본 논문에서는 임플란트주위염 처치에 있어 레이저가 갖는 효능에 대한 최근 연구 결과들을 문헌고찰을 통해 되짚어보고자 한다.

• 생약학회지
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• 제45권1호
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• pp.1-10
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• 2014

Ginsenoside Rg3 (G-Rg3) is one of protopanaxadiol ginsenosides characteristic of red ginseng, steamed and dried ginseng (Panax ginseng), which has recently attracted much attention for its antitumor properties in vitro and in vivo animal models. Experimental studies have demonstrated that it could promote cancer cell apoptosis, inhibit cancer cell growth, the apoptosis of cancer cells, adhesion, invasion and metastasis, and also prevent an angiogenetic formation in prostate, breast, ovarian, colorectal, gastric, liver and lung cancer etc. It has shown the antitumor activities by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins), growth factors (vascular endothelial growth factor), tumor suppressors (p53 and p21), cell death mediators (caspases, Bcl-2, Bax), inflammatory response molecules ($NF-{\kappa}B$ and COX-2), protein kinases (JNK, Akt, and AMP-activated protein kinase) and Wnt/${\beta}$-catenin signaling. In addition, the combination of Rg3 and chemotherapeutic agents have synergistically enhanced therapeutic efficacy and reduced antagonistically side effects. Furthermore, it can reverse the multidrug resistance of cancer cells, prolong the survival duration and improve life quality of cancer patients. Taken together, accumulating evidences could provide the potential of G-Rg3 in the treatment of cancers and the feasibility of further randomized placebo controlled clinical trials.

• Journal of Microbiology and Biotechnology
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• 제28권9호
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• pp.1563-1572
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• 2018

Gold nanoparticles (AuNP) and their conjugates have been gaining a great deal of recognition in the medical field. Meanwhile, extended-spectrum ${\beta}$-lactamases (ESBL)-producing bacteria are also demonstrating a challenging problem for health care. The aim of this study was the biosynthesis of AuNP using Rosa damascenes petal extract and conjugation of ceftriaxone antibiotic (Cef-AuNP) in inhibiting ESBL-producing bacteria and study of in vitro anticancer activity. Characterization of the synthesized AuNP and Cef-AuNP was studied. ESBL-producing strains, Acinetobacter baumannii ACI1 and Pseudomonas aeruginosa PSE4 were used for testing the efficacy of Cef-AuNP. The cells of MCF-7 breast cancer were treated with previous AuNP and Cef-AuNP at different time intervals. Cytotoxicity effects of apoptosis and its molecular mechanism were evaluated. Ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy established the formation of AuNP and Cef-AuNP. Transmission electron microscope demonstrated that the formed nanoparticles were of different shapes with sizes of 15~35 nm and conjugation was established by a slight increase in size. Minimum inhibitory concentration (MIC) values of Cef-AuNP against tested strains were obtained as 3.6 and $4{\mu}g/ml$, respectively. Cef-AuNP demonstrated a decrease in the MIC of ceftriaxone down to more than 27 folds on the studied strains. The biosynthesized AuNP displayed apoptotic and time-dependent cytotoxic effects in the cells of MCF-7 at a concentration of $0.1{\mu}g/ml$ medium. The Cef-AuNP have low significant effects on MCF-7 cells. These results enhance the conjugating utility in old unresponsive ceftriaxone with AuNP to restore its efficiency against otherwise resistant bacterial pathogens. Additionally, AuNP may be used as an alternative chemotherapeutic treatment of MCF-7 cancer cells.

• Journal of Pharmaceutical Investigation
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• 제35권4호
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• pp.249-254
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• 2005

Multidrug resistance (MDR) of cancer cells is, at least in part, associated with the overexpression of P-glycoprotein (P-gp). Many studies have demonstrated that natural compounds obtained from fruits, vegetables, teas and medicinal plants may modulate P-gp activity. The objective of the present investigation was to examine the effect of seven natural compounds on the P-gp activity in human uterine sarcoma cell line, MES-SA/DX5. Daunomycin uptake was significantly increased by biochanin A and silymarin (p<0.0001) whereas it was reduced by morin (p<0.01). The efflux of daunomycin from the cells was significantly inhibited by biochanin A, morin, cephalotaxine, berberine (p<0.05) and silymarin (p<0.0001). Biochanin A, berberine and silymarin significantly decreased $IC_{50}$ value of daunomycin (p<0.05) while morin increased it (p<0.05). These results suggest that some natural compounds such as biochanin A and silymarin may inhibit P-gp function and can be developed as MDR reversing agents to improve the efficacy of chemotherapeutic drugs when administered concomitantly.

• Journal of Microbiology and Biotechnology
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• 제23권9호
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• pp.1339-1346
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• 2013

Conventional chemotherapeutic regimens often accompany severe side effects and fail to induce complete regression of chemoresistant or relapsing metastatic cancers. The need for establishing more efficacious anticancer strategies led to the development of a combined modality treatment of chemotherapy in conjunction with immunotherapy or radiotherapy. It has been reported that poly-gamma-glutamate (${\gamma}$-PGA), a natural polymer composed of glutamic acids, increases antitumor activity by activating antigen-presenting cells and natural killer (NK) cells. Here, we investigated the antitumor effect of ${\gamma}$-PGA in combination with cyclophosphamide in a murine melanoma model. Whereas cyclophosphamide alone directly triggered apoptosis of tumor cells in vitro, ${\gamma}$-PGA did not show cytotoxicity in tumor cells. Instead, it activated macrophages, as reflected by the upregulation of surface activation markers and the secretion of proinflammatory factors, such as nitric oxide and tumor necrosis factor ${\alpha}$. When the antitumor effects were examined in a mouse model, combined treatment with cyclophosphamide and ${\gamma}$-PGA markedly suppressed tumor growth and metastasis. Notably, ${\gamma}$-PGA treatment dramatically increased the NK cell population in lung tissues, coinciding with decreased metastasis and increased survival. These data collectively suggest that ${\gamma}$-PGA can act as an immunotherapeutic agent that exhibits a synergistic antitumor effect in combination with conventional chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6513-6519
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• 2015

Background: Recent attention on chemotherapeutic intervention against cancer has been focused on discovering and developing phytochemicals as anticancer agents with improved efficacy, low drug resistance and toxicity, low cost and limited adverse side effects. In this study, we investigated the effects of Curcuma C20-dialdehyde on growth, apoptosis and cell cycle arrest in colon and cervical cancer cell lines. Materials and Methods: Antiproliferative, apoptosis induction, and cell cycle arrest activities of Curcuma C20-dialdehyde were determined by WST cell proliferation assay, flow cytometric Alexa fluor 488-annexin V/propidium iodide (PI) staining and PI staining, respectively. Results: Curcuma C20 dialdehyde suppressed the proliferation of HCT116, HT29 and HeLa cells, with IC50 values of $65.4{\pm}1.74{\mu}g/ml$, $58.4{\pm}5.20{\mu}g/ml$ and $72.0{\pm}0.03{\mu}g/ml$, respectively, with 72 h exposure. Flow cytometric analysis revealed that percentages of early apoptotic cells increased in a dose-dependent manner upon exposure to Curcuma C20-dialdehyde. Furthermore, exposure to lower concentrations of this compound significantly induced cell cycle arrest at G1 phase for both HCT116 and HT29 cells, while higher concentrations increased sub-G1 populations. However, the concentrations used in this study could not induce cell cycle arrest but rather induced apoptotic cell death in HeLa cells. Conclusions: Our findings suggest that the phytochemical Curcuma C20-dialdehyde may be a potential antineoplastic agent for colon and cervical cancer chemotherapy and/or chemoprevention. Further studies are needed to characterize the drug target or mode of action of the Curcuma C20-dialdehyde as an anticancer agent.