• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3351-3355
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• 2013

Photodynamic therapy (PDT) is a promising cancer treatment modality that uses dye-sensitized photooxidation of biologic matter in target tissue. This study explored effects of the photosensitizer BCPD-17 during PDT for osteosarcoma. LM-8 osteosarcoma cells were treated with BCPD-17 and cell viability after laser irradiation was assessed in vitro with the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of BCPD-17 during PDT recurrence were then examined on tumor-bearing mice in vivo. BCPD-17 had dosedependent cytotoxic effects on LM-8 osteosarcoma cells after laser irradiation which also had energy-dependent effects on the cells. The rate of local recurrence was reduced when marginal resection of mice tumors was followed by BCPD-17-mediated PDT. Our results indicated BCPD-17-mediated PDT in combination with marginal resection of tumors is a potentially new effective treatment for osteosarcoma.

• 한국한의학연구원논문집
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• 제2권1호
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• pp.269-288
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• 1996

Coicis Semen is one of the oriental medicine that has been used for the treatment of the diseases such as pulmonary abscess, periappendicular abscess and wart since ancient times. However, the mechanism of the action of the drug is not well studied. This study was done to investigate the effects of Coicis Semen on the host defence mechanism. Effects of Coicis Semen on the immune responses were analysed by measuring the contact hypersensitivity, hemagglutinin, hemolysin and rosette formation, cytotoxicity, and reactive oxygen intermidiates production. As the results, water extract of Coicis Semen administration enhanced the antibodies (hemagglutinin and hemolysin) formation and the appearance of rosette forming cells of the spleen. Also Coicis Semen increased the allogeneic immune response in the mouse, showed cytotoxic activity against human leukemia cell line(K562) and decreased the contact hypersensitivity against dinitroflurobenzene. Also administration of Coicis Senlen slightly increased NK cell activity and enhanced the production of such reactive oxygen intermediates as superoxide and hydrogen peroxide from the macrophages in vivo and in vitro. The above results demonstrate that Coicis Semen has enhancing effects on cellular and humoral immune responses against disease.

• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.290-297
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• 2021

Leptolyngbya sp. KIOST-1 (LK1) is a newly isolated cyanobacterium that shows no obvious cytotoxicity and contains high protein content for both human and animal diets. However, only limited information is available on its toxic effects. The purpose of this study was to validate the safety of LK1 powder. Following Organisation for Economic Co-operation and Development (OECD) guidelines, a single-dose oral toxicity test in Sprague Dawley rats was performed. Genotoxicity was assessed using a bacterial reverse mutation test with Salmonella typhimurium (strains TA98, TA100, TA1535, and TA1537) and Escherichia coli WP2 uvrA, an in vitro mammalian chromosome aberration test using Chinese hamster lung cells, and an in vivo mammalian erythrocyte micronucleus test using Hsd:ICR (CD-1) SPF mouse bone marrow. After LK1 administration (2,500 mg/kg), there were no LK1-related body weight changes or necropsy findings. The reverse mutation test showed no increased reverse mutation upon exposure to 5,000 ㎍/plate of the LK1 powder, the maximum tested amount. The chromosome aberration test and micronucleus assay demonstrated no chromosomal abnormalities and genotoxicity, respectively, in the presence of the LK1 powder. The absence of physiological findings and genetic abnormalities suggests that LK1 powder is appropriate as a candidate biomass to be used as a safe food ingredient.

• Journal of Ginseng Research
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• 제46권6호
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• pp.771-779
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• 2022

Background: As a kind of common complication of the surgery of perianal diseases, perianal ulcer is known as a nuisance. This study aims to develop a kind of 20(S)-ginsenoside Rg3 (Rg3)-loaded hydrogel to treat perianal ulcers in a rat model. Methods: The copolymers PLGA₁₆₀₀-PEG₁₀₀₀-PLGA₁₆₀₀ were synthesized by ring-opening polymerization process and Rg3-loaded hydrogel was then developed. The perianal ulcer rat model was established to analyze the treatment efficacy of Rg3-loaded hydrogel for ulceration healing for 15 days. The animals were divided into control group, hydrogel group, free Rg3 group, Rg3-loaded hydrogel group, and Lidocaine Gel® group. The residual wound area rate was calculated and the blood concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) were recorded. Hematoxylin and eosin (H&E) staining, Masson's Trichrome (MT) staining, and tumor necrosis factor α (TNF-α), Ki-67, CD31, ERK1/2, and NF-κB immunohistochemical staining were performed. Results: The biodegradable and biocompatible hydrogel carries a homogenous interactive porous structure with 10 ㎛ pore size and five weeks in vivo degradation time. The loaded Rg3 can be released sustainably. The in vitro cytotoxicity study showed that the hydrogel had no effect on survival rate of murine skin fibroblasts L929. The Rg3-loaded hydrogel can facilitate perianal ulcer healing by inhibiting local and systematic inflammatory responses, swelling the proliferation of nuclear cells, collagen deposition, and vascularization, and activating ERK signal pathway. Conclusion: The Rg3-loaded hydrogel shows the best treatment efficacy of perianal ulcer and may be a candidate for perianal ulcer treatment.

• 한국식품과학회지
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• 제44권3호
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• pp.343-349
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• 2012

한국 전통발효음료 중에 존재하는 특이 다당류의 화학적 특성 및 생물활성을 규명할 목적으로, 농가에서 직접 발효한 복분자주로부터 다당류를 분리하고 이들의 각종 면역증강활성에 대해 검토하였다. 복분자주에 80% ethanol 침전을 행하여 얻어진 조다당획분 RB-0를 이용, 연속적인 3회의 column chromatography를 행하여, 복분자주의 주요 다당인 RB-1b-I으로 정제할 수 있었다. RB-1b-I획분은 HPLC상에서 대칭을 유지하는 단일 peak로 검출되었으며, 분자량은 약 180 kDa으로 평가되었다. 정제다당인 RB-1b-I의 구성당 조성을 확인한 결과, mannose가 76.8%로 주를 이루고 있었으며, 그 외에 galactose(15.8%), arabinose(3.8%), glucose(2.6%) 및 rhamnose(1.2%)의 순으로 함유되어 있었다. 이러한 결과는 복분자 중에 존재하는 주 다당이 발효 효모의 세포벽에서 기원한 mannan임을 추정하게 하였다. 한편 복분자주에서 정제한 다당 RB-1b-I은 in vitro상에서 macrophage의 활성화를 높은 비율로 유도하였으며, 비장세포에 대해 높은 증식능을 보였다. 또한 RB-1b-I을 정맥 투여한 경우, NK cell을 활성화하여 YAC-1 종양세포에 대한 세포독성을 증가시킴이 관찰되었다. 한편 고분자 정제 다당인 RV-1b-I은 비특이적 면역계에 있어 중요 역할을 담당하고 있는 보체계에 대하여 농도 의존적인 활성화 경향을 보였다. 이들은 Ca++ 이온이 제거된 상태에서의 항보체 활성과 antihuman C3를 이용한 2차원 면역전기영동에 의하여 C3 산물을 동정한 결과로부터 보체계의 classical pathway와 alternative pathway양 경로를 모두 경유하여 활성을 나타냄을 확인할 수 있었다. 이상의 결과로부터 복분자주에는 인체 건강에 유익한 면역증진 활성을 제공하는 다당류가 함유되어 있음을 알 수 있었다.

• 대한화장품학회지
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• 제43권2호
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• pp.115-124
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• 2017

레조시놀다이펜틸에터(1,3-di(pentyloxyl)benzene)의 피부 미백 효과를 확인하기 위해 in vitro 실험을 통하여 미백 효과를 평가하였다. 레조시놀다이펜틸에터는 resorcinol과 1-bromopentane의 알킬화반응을 통하여 제조하였으며, 반응 결과물을 NMR, MS 등의 분석장비를 통해 확인하였다. 레조시놀다이펜틸에터의 피부 안전성 평가를 위하여, 피부를 구성하는 세포들(keratinocyte, melanocyte, fibroblast)에 대한 독성을 분석한 결과 대조군에 비해서 모든 세포주들에서 유사한 cell viability를 확인하였다. 세포생존에 영향을 미치지 않는 농도인 $20{\mu}g/mL$에서 세포 외 멜라닌 분비 저해능을 측정한 결과 $20{\mu}g/mL$ 농도에서 약 65.75%까지 농도 의존적으로 멜라닌 분비를 억제하는 것을 확인하였으며, 세포 내 멜라닌 생성 억제율을 측정한 결과에서도 약 53.89%를 억제함을 확인하였다. 멜라닌 형성 관련 티로시나제, TRP-1, TRP-2의 mRNA 발현량과 단백질 발현량을 real-time PCR 방법과 western blot으로 측정을 한 결과 레조시놀다이펜틸에터는 멜라닌 억제효과가 전사(transcription)단계부터 억제하는 것을 확인하였다. 최종적으로 본 연구는 레조시놀다이펜틸에터의 미백기능성화장품 신소재로서의 적용가능성을 제시하였다.

• 한국약용작물학회지
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• 제18권3호
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• pp.143-150
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• 2010

This study showed the increase of antitumor activities of water soluble E. sinica extract by nano-encapsulation process with lecithin. Five groups of lecithin only group (LO), lecithin nano-encapsulated E. sinica group (LE), E. sinica only group (EO), one negative control group (NCO) and positive control group (PCO) were set for several anticancer experiment and fed into Sarcoma-180 injected mice. The cytotoxicity of LE on the human normal kidney cell (HEK293) showed 14.8% lower than 19.2% of EO and 18.4% of LO. Growth of human liver carcinoma cell and human stomach carcinoma cell as representative of digestive system in vitro was inhibited up to about 85.1% and 87.3%, in adding 1.0 mg/$m{\ell}$ of LE, which values 15% higher than that from conventional EO. The survival rates of each mice group were 40%, 63%, 48%, 33% and 100%, respectively after 40 days of injecting Sarcoma-180. The increment of their body weights of the extract feeding groups was suppressed down to 10~15%, compared to the negative control. The nano-particles also reduced the hypertrophy of the internal organs such as spleen and liver down to 15~20%, compared to those as the other groups. Among them, LE effectively reduced the size of tumor form to 20%. From these results, in vitro and in vivo antitumor activities of E. sinica could be enhanced by using nano-encapsulation process with lecithin because of better permeation into the cancer cells by confocal observations.

• 폴리머
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• 제38권1호
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• pp.54-61
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• 2014

Bombyx mori silk fibroin(SF)과 블렌드 필름을 만들기 위하여 키토산에 1,3-propanesultone을 반응시켜 수용성 sulfobetaine chitosan(SCs)을 제조하였다. 여러 가지 비율의 SF/SCs 블렌드 필름을 B. mori SF와 SCs의 수용액을 혼합하여 제조하였다. 수용액으로부터 얻어진 SF/SCs 블렌드 필름의 구조와 형태 변화는 분광학적 및 열적 분석을 통해 규명하였다. SF와 SCs의 혼합 비율에 따른 인공 피부나 화상치료 목적의 비이오재료로서의 물리적 및 기계적 성질에 미치는 영향을 조사하였다. X-선 분석으로 두 생체고분자 사이에 좋은 친화성을 보여주고 있음을 알 수 있었으며 기계적 성질도 SCs의 함량이 증가하면 크게 증가하였다. $37^{\circ}C$에서 phosphate buffered saline solution 용액 중에서 in vitro 분해 실험을 8주 동안 시행한 결과 46.4%가 분해됨을 알 수 있었다. MC3T3-E1 세포에 의한 독성 실험 결과 무독성을 나타내 주었으며, 3일의 배양 후 SF/SCs 필름의 상대 세포 수는 최적화된 tissue culture plastic보다 약간 낮게 나타남을 알 수 있었다.

• Journal of Oral Medicine and Pain
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• 제34권3호
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• pp.261-276
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• 2009

Sreptomyces라는 세균에서 추출한 lactacystin은 선택적인 proteasome 억제제로서 많은 연구에서 사용되어져 왔다. Proteasome 억제제는 최근의 많은 연구를 통해서 암세포증식의 억제에 대한 효과가 증명되었으며, 특히 다른 항암제와 병용처리 시, 상호작용에 의한 상승효과가 있다고 알려져 있다. 현재 proteasome 억제제는 새로운 강력한 항암제로서 분류되어 있다. 본 연구는 사람혀편평세포암종세포(SCC25 cells)에서 lactacystin의 세포독성과 성장억제 효과, 그리고 세포자멸사의 유도에 대한 분자생물학적 기전을 밝히기 위해 실험을 시행하였다. SCC25 세포, 사람정상각화세포 (HaCaT cells) 그리고 사람치은섬유모세포(HGF-1 cells)의 생존율 측정은 MTT법을 시행하였고, SCC25 세포의 성장억제를 확인하기 위해서는 clonogenic assay를 사용하였다. lactcystin이 SCC25 세포에서 세포자멸사가 유도되는지를 확인하기 위해서 hoechst 염색법, hemacolor 염색법 그리고 TUNEL법을 시행하였다. 그리고 SCC25 세포에 lactacystin을 적용한 후, Western blot 분석, 세포면역화학염색, 공초점레이저주사현미경 검경, FACScan flow cytometry, 사립체막 전위변화, proteasome 활성도 측정 등을 시행하였다. Lactacystin으로 처리된 SCC25 세포는 시간 및 용량 의존적인 세포생존율의 감소, 용량의존적인 세포성장억제 그리고 세포자멸사에 의한 세포죽음을 보였다. 흥미롭게도 lactacytin은 정상세포인 HaCat 세포와 HGF-1 세포에서는 세포독성을 전혀 보이지 않았다. 그리고 lactacystin이 적용된 SCC25세포에서 핵 응축, DNA의 조각남, 사립체막전위와 proteasome 활성도의 감소, DNA 양의 감소, cytochrome c의 사립체에서의 세포질로의 유리, AIF와 DFF40 (CAD)의 핵으로의 이동, Bax의 증가, caspase-7, caspase-3, PARP, lamin A/C 그리고 DFF45 (ICAD)의 활성화 혹은 파괴와 같은 아주 다양한 세포자멸사 증거를 보였다. Flow cytometry 분석에서는 CDK 억제제인 $p21^{WAF1/CIP1}$와 $p27^{KIP1}$의 발현 증가와 관계있는 것으로 추정되어 지는 G1 세포주기 정지를 보였다. 이러한 결과는 lactacytin이 SCC25 세포에서 G1 세포주기정지와 proteasome, 사립체 및 caspase 경로의 연속반응을 통한 세포자멸사를 유도함을 명확하게 증명하고 있다. 이와 같은 세포주기 정지와 세포자멸사 유도능은 lactacytin이 사람혀편평상피세포암종의 새로운 치료전략으로서의 가능성을 제공한다고 생각한다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7179-7188
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• 2015

Cancer is a major health obstacle around the world, with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) as major causes of morbidity and mortality. Nowadays, there isgrowing interest in the therapeutic use of natural products for HCC and CRC, owing to the anticancer activity of their bioactive constituents. Boswellia serrata oleo gum resin has long been used in Ayurvedic and traditional Chinese medicine to alleviate a variety of health problems such as inflammatory and arthritic diseases. The current study aimed to identify and explore the in vitro anticancer effect of B. Serrata bioactive constituents on HepG2 and HCT 116 cell lines. Phytochemical analysis of volatile oils of B. Serrata oleo gum resin was carried out using gas chromatography-mass spectrometry (GC/MS). Oleo-gum-resin of B. Serrata was then successively extracted with petroleum ether (extract 1) and methanol (extract 2). Gas-liquid chromatography (GLC) analysis of the lipoidal matter was also performed. In addition, a methanol extract of B. Serrata oleo gum resin was phytochemically studied using column chromatography (CC) and thin layer chromatography (TLC) to obtain four fractions (I, II, III and IV). Sephadex columns were used to isolate ${\beta}$-boswellic acid and identification of the pure compound was done using UV, mass spectra, $^1H$ NMR and $^{13}C$ NMR analysis. Total extracts, fractions and volatile oils of B. Serrata oleo-gum resin were subsequently applied to HCC cells (HepG2 cell line) and CRC cells (HCT 116 cell line) to assess their cytotoxic effects. GLC analysis of the lipoidal matter resulted in identification of tricosane (75.32%) as a major compound with the presence of cholesterol, stigmasterol and ${\beta}$-sitosterol. Twenty two fatty acids were identified of which saturated fatty acids represented 25.6% and unsaturated fatty acids 74.4% of the total saponifiable fraction. GC/MS analysis of three chromatographic fractions (I,II and III) of B. Serrata oleo gum resin revealed the presence of pent-2-ene-1,4-dione, 2-methyl- levulinic acid methyl ester, 3,5- dimethyl- 1-hexane, methyl-1-methylpentadecanoate, 1,1- dimethoxy cyclohexane, 1-methoxy-4-(1-propenyl)benzene and 17a-hydroxy-17a-cyano, preg-4-en-3-one. GC/MS analysis of volatile oils of B. Serrata oleo gum resin revealed the presence of sabinene (19.11%), terpinen-4-ol (14.64%) and terpinyl acetate (13.01%) as major constituents. The anti-cancer effect of two extracts (1 and 2) and four fractions (I, II, III and IV) as well as volatile oils of B. Serrata oleo gum resin on HepG2 and HCT 116 cell lines was investigated using SRB assay. Regarding HepG2 cell line, extracts 1 and 2 elicited the most pronounced cytotoxic activity with $IC_{50}$ values equal 1.58 and $5.82{\mu}g/mL$ at 48 h, respectively which were comparable to doxorubicin with an $IC_{50}$ equal $4.68{\mu}g/mL$ at 48 h. With respect to HCT 116 cells, extracts 1 and 2 exhibited the most obvious cytotoxic effect; with $IC_{50}$ values equal 0.12 and $6.59{\mu}g/mL$ at 48 h, respectively which were comparable to 5-fluorouracil with an $IC_{50}$ equal $3.43{\mu}g/mL$ at 48 h. In conclusion, total extracts, fractions and volatile oils of B. Serrata oleo gum resin proved their usefulness as cytotoxic mediators against HepG2 and HCT 116 cell lines with different potentiality (extracts > fractions > volatile oil). In the two studied cell lines the cytotoxic acivity of each of extract 1 and 2 was comparable to doxorubicin and 5-fluorouracil, respectively. Extensive in vivo research is warranted to explore the precise molecular mechanisms of these bioactive natural products in cytotoxicity against HCC and CRC cells.