In this study, we investigated the effect of the extracts from Vaccinium oldhamii on cell proliferation and the regulatory mechanisms of cyclin D1 protein level in human cancer cells. The branch extracts from Vaccinium oldhamii (VOB) showed higher inhibitor effect against the cell growth than leave extracts (VOL) and fruit extracts (VOF) in human colorectal cancer, breast cancer, prostate cancer, non-small lung cancer, pancreatic cancer and liver cancer cells. In addition, VOB decreased cyclin D1 level at both protein and mRNA level. MG132 treatment attenuated VOB-mediated cyclin D1 downregulation. A point mutation of threonine-286 to alanine attenuated cyclin D1 degradation by VOB. In addition, the inhibition of nuclear export by leptomycin B (LMB) attenuated cyclin D1 degradation by VOB. But, the treatment of PD98059 (ERK1/2 inhibitor), SB203580 (p38 inhibitor), SP600125 (JNK inhibitor), LiCl (GSK3β inhibitor), LY294002 (PI3K inhibitor) or BAY 11-7082 (IκK inhibitor) did not affect VOB-induced cyclin D1 degradation. In conclusion, VOB induced cyclin D1 degradation through redistribution of cyclin D1 from the nucleus to cytoplasm via T286 phosphorylation of cyclin D1, which resulted in the inhibition of cancer cell proliferation.

Background : This study was conducted to investigate the antioxidant activities and anticancer effect in 80% ethanol extract from foxtail millet (Setaria italica) and proso millet (Panicum miliaceum) and sorghum (Sorghum bicolor) varieties. Methods and Results : These extracts were evaluated for contents of total polyphenol and antioxidant activities using DPPH and ABTS radical scavenging activities. In concentration of 1000 ㎍/㎖, total polyphenol contents of foxtail millet, proso millet and sorghum were 7.68 - 12.74 ㎍․GAE/㎖, 13.01 - 14.79 ㎍․GAE/㎖ and 48.24 - 62.33 ㎍․GAE/㎖, respectively. Sorghum extracts showed strong radical scavenging activity comparable to well-known antioxidant, trolox. Anticancer effect was evaluated for MTT assay using AGS human gastric cancer cells. All extracts decreased growth of AGS cancer cells. Foxtail millet extracts were decreased about 40% of cell viability in all concentrations. Sorghum extracts were decreased cell viability, concentration dependent manner. Especially, Donganme extract (one of the sorghum variety) was the highest anti cancer effect under AGS cancer cells. Conclusion : Based on these results, millet and sorghum has potential health promoting bioactive compounds as functional food.

Background : Ginseng, one of most famous traditional oriental medicines, has been known for a number of pharmacological properties including anti-tumor, anti-diabetic, anti-fatigue, anti-stress, anti-oxidative, and anti-aging effects. 20(S)-Protopanaxadiol (PPD), a intestinal metabolite of ginsenosides, is one of the active ingredients in ginseng. In this study, we investigated the synergistic anticancer effect of 20(S)-PPD and temozolomide (TMZ) and the mechanism of 20(S)-PPD on glioblastoma cells. Methods and Results : We examined cell viability and the morphological changes of C6 cells after treatment of 20(S)-PPD and TMZ. 20(S)-PPD showed a potent antiproliferative activity against C6 cells by triggering apoptosis. 20(S)-PPD-induced apoptosis was characterized by a dose-dependent mitochondrial damage. 20(S)-PPD and TMZ had a synergistic effect in increasing mitochondrial damage via caspase 3 activation. Conclusion : These results revealed an unexpected mechanism of 20(S)-PPD and TMZ, triggering a mitochondrial-mediated apoptosis in C6 cells. Our findings encourage further studies of 20(S)-PPD as a promising chemopreventive agent against glioblastoma.

The purpose of this study was to determine the content of phenolics and various anthocyanin compounds, and antioxidant and anticancer activities of the extracts from pomergranates, which were produced in two different regions including Goheung, Korea and California, USA. These pomergrantes were divided into juice, pericarp, and seed parts and each part was extracted with 95% methanol. Content of total phenolics [mg chlorogenic acid equivalents/kg DW] was highest in pericarp, followed by juice and seeds from pomergrantes in both regions. The anthocyanins identified in pomegranate fruit were cyanidin-3,5-diglucoside chloride (Cy3,5G), cyanidin-3-O-glucoside chloride (Cy3G), delphini din-3,5-di-O-glucoside chloride (Dp3,5G), delphinidin-3-O-glucoside chloride (Dp3G), pelargonidin- 3,5-di-glucoside chloride (Pg3,5G), and pelargonidin-3-glucoside chloride (Pg3G). Among these, cyanidin-3, 5-diglucoside chloride (Cy3,5G) was the major anthocyanin in California pomegranate fruit juice and Goheung pomegranate fruit pericarp. DPPH (1,1-diphenyl-2-picryl hydrazyl radical) free radical scavenging activity was dose-dependently increased, and was higher in pericarp part than juice or seed parts from pomergrantes in both regions. By MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, pericarp extracts from pomergrantes in both regions showed the highest anticancer activity, which was higher on Calu-6 for human pulmonary carcinoma than SNU-601 for human gastric carcinoma. Correlation between polyphenols and anticancer activity on Calu-6 was determined to be in the range of r2=0.8904 to 0.9706.

The seed of safflower (Carthamus tinctorius L) has been reported to suppress human cancer cell proliferation. However, the mechanisms by which safflower seed inhibits cancer cell proliferation have remained nuclear. In this study, the inhibitory effect of the safflower seed (SS) on the proliferation of human colorectal cancer cells and the potential mechanism of action were examined. SS inhibited markedly the proliferation of human colorectal cancer cells (HCT116, SW480, LoVo and HT-29). In addition, SS suppressed the proliferation of human breast cancer cells (MDA-MB-231 and MCF-7). SS treatment decreased cyclin D1 protein level in human colorectal cancer cells and breast cancer cells. But, SS-mediated downregulated mRNA level of cyclin D1 was not observed. Inhibition of proteasomal degradation by MG132 attenuated cyclin D1 downregulation by SS and the half-life of cyclin D1 was decreased in SS-treated cells. In addition, SS increased cyclin D1 phosphorylation at threonine-286 and a point mutation of threonine-286 to alanine attenuated SS-mediated cyclin D1 degradation. Inhibition of ERK1/2 by PD98059 suppressed cyclin D1 phosphorylation and downregulation of cyclin D1 by SS. In conclusion, SS has anti-proliferative activity by inducing cyclin D1 proteasomal degradation through ERK1/2-dependent threonine-286 phosphorylation of cyclin D1. These findings suggest that possibly its extract could be used for treating colorectal cancer.

Background : Oxidative stress-related iflammatory mechanisms may play an important role in the pathogenesis of cisplatin-induced nephrotoxicity. Safflower (Carthamus tinctorius L.) seed is a crude drug rich in serotonin derivatives to exhibit several biological activities, including antioxidant, anti-inflammation and anti-cancer effects. The purpose of this study was to determine the renoprotective effects of Safflower seed, using cisplatin-induced nephrotoxicity mice. Methods and Results : Safflower seed was orally administered at a dose of 100 and 200 mg/kg body weight for 5 days before the intraperitoneal injection of cisplatin 20 mg/kg body weight, and the effects were compared with those of vehicle-treated cisplatin administered to control and normal mice. In the serum and kidney, renal function parameters reactive oxygen species and expression of protein related to oxidative stress, DNA damage, inflammation and apoptosis were examined. Safflower seed treatment attenuated serum BUN, createinine and renal oxidative stress through reduction of reactive oxygen species and increase in the protein expression level of catalase. Safflower seed reduced renal protein expression of p-p38 and p-JNK (mitogen-activated protein kinase pathway), pro-apoptotic factors (such as Bax and caspase 3) and nuclear factor-kappa B-targeting pro-inflammatory cyclooxygenase-2 and inducible nitric oxide synthase. In addition, Safflower seed treatment led to significantly attenuated histological damage in the kidney. Conclusion : These renoprotective effects of Safflower seed were achieved through attenuation of oxidative stress and its sensitive protein expression associated with inflammation and apoptosis in cisplatin-induced nephrotoxicity mice.

This study aims to evaluate the antitumor effect of Adonis multiflora, one of the plants in the Ranunculaceae, on mice to which hepatoma cells were transplanted and to suggest its possibility as a candidate natural substance to replace antitumor drugs. We performed the MTT assay to assess the extract had a decrease in the growth rate of hepatoma cells depending on concentration. In particular, 100 ㎍/㎖ of the extract showed 40% of growth retardation rate. We assessed the autophagy activity to identify the inhibitory autophagy mechanism of tumor cells in the extract. This proved that the activity increases more as the concentration of the extract is higher. We conducted the Western blot test to confirmed the expression of two proteins LC3 and p62. The expression of p62 was in inverse proportion to the concentration of the extract whereas LC3-Ⅱ increased more as the concentration of the extract was higher. This showed that an increase in the autophagy relies on the conentration of the extract. We performed a test to discover the influence of the extracts on hepatoma cells transplanted to mice. The test proved that the extract triggers a significant decrease in the growth rate of tumor cells. Compared to the start of the test, the size of tumor cells with 50, 100 and 200 ㎎/㎏ of the extract respectively increased by 4, 3.7 and 3.5 times whereas in the controlling group by 6.3 times. The size of tumor cells in benign tumor controlling group increased by 3.1 times. This showed a significant decrease in the growth rate of tumor cells compared to the controlling group. We carried out the experiment of influence of the extract on the expression of two proteins LC3 and p62 in the tumor tissue transplanted into mice. The experiment showed that LC3-II increases more as the concentration of the extract is higher. However, there was a rapid decrease in p62 with 200 ㎎/㎏ of the extract compared to the controlling group. In this study, we proved that the autophagy activity of Adonis multiflora extract inhibits the growth of hepatoma cells by in vitro and in vivo experiments. In conclusion, the inhibitory autophagy mechanism of tumor cells in the extract can be used as a new treatment of antitumor.

Lepisorus thunbergianus (Kaulf.) Ching has been used in folk medicine in Korea. In this study, a L. thunbergianus methanol extract and its fractions were investigated for their antioxidant properties. The results showed that the ethyl acetate and butanol fractions of L. thunbergianus possess potent DPPH radical scavenging activities. Both fractions also possessed reducing power and inhibited reactive oxygen species formation. In addition, the cytotoxic activity of the L. thunbergianus n-hexane fraction (HF) was investigated. The results suggested that the HF remarkably suppressed proliferation of human breast, liver and colon cancer cells. These results demonstrate, for the first time, that L. thunbergianus extract induces apoptosis in SW620 cells, suggesting that L. thunbergianus may have potential as a therapeutic agent for colon cancer.

본 연구에서 고추장 제조시 발효가 항돌연변이 효과와 in vitro 항암효과에 미치는 영향을 확인하기 위하여 고추장 제조 재료인 원료 밀, 1차발효밀, 2차발효밀, 최종발효밀, 고춧가루와 최종발효밀로 제조된 고추장의 Sal. Typhimurium TA100을 이용한 Ames test를 실시하여 MNNG에 대한 항돌연변이 효과를 살펴보았으며, HT-29 인체 대장암세포와 AGS 인체 위암세포의 성장 억제효과를 살펴보았다. 실험한 결과 원료 밀보다 1차발효밀, 2차발효밀보다 최종발효밀이 발효진행에 따라 점차 증진된 항돌연변이 효과와 in vitro 항암효과가 나타났으며 최종발효밀과 고춧가루로 제조된 고추장이 가장 높았다. 15, 30일 발효시킨 고추장이 발효되지 않은 고추장보다 더 높은 항암효과가 나타났다. 따라서 발효과정(기간)이 고추장의 항돌연변이 효과와 항암효과에 중요하게 관련되어 있다고 할 수 있으며 고추장의 주재료인 고춧가루의 capsaicin, 비타민C와 β-carotene 등의 작용만이 아닌 밀에서 온 발효 숙성 중에 많이 증식된 미생물 그리고 발효에 의한 생성된 다른 활성물질이 항돌연변이와 항암 효과에 관련되어 있다고 하겠다.

The biological activities of Smilax china L. rhizome (SCR), hot water (SCRW) and 70% ethanol extract (SCRE) were analyzed. The total phenolic contents of SCRW and SCRE were 51.7 and 100.5 mg/g, respectively. The measured flavonoid content of SCRW (61.7 μg/g) was almost double that of SCRE (31.7 μg/g). SCRE (IC50=42.4 μg/mL) exhibited stronger antioxidant activity in the DPPH system than the positive control α-tocopherol (71.3 μg/mL) or butylated hydroxy anisole (53.8 μg/mL) did. SCRE (IC50=50.3 μg/mL) also showed stronger ABTS radical scavenging activity, as did α-tocopherol (67.1 μg/mL). The SOD-like activity and Tyrosinase inhibition activity of SCRW and SCRE showed almost the same pattern. The best SOD-like activity and tyrosinase inhibition activity were measured as 24.9% and 20.3% in SCRW at 1,000 μg/mL, respectively. The cytotoxic effects of the SCR extracts were analyzed via MTT assay on human cancer and normal cells. SCRW and SCRE did not show cytotoxicity up to the concentration of 1,000 μg/mL against the normal human cell line HEK293. Against human breast cancer cells (MCF-7), SCRW inhibited MCF-7 growth (by 27.6%) better than the anticancer drug cyclophosphamide (15.5%) at 1,000 μg/mL. SCRE (1,000 μg/mL) inhibited the growth of human lung cancer cells A549 (37.6%) and human stomach cancer cells AGS (53.6%) more effective than did SCRW (21.0% and 35.4%) or CPA (22.2% and 31.7%). These results suggest the potential use of SCRE and SCRW as an excellent antioxidant and antiproliferative substance, respectively.

참외 종자의 기능성을 규명하는 연구의 일환으로 항암활성을 조사하고자 하였다. 추출용매에 따른 항암활성을 조사하고자 헥산, 에탄올, 물 등 다양한 추출용매를 사용하여 참외 종자 추출물을 제조하였고, 가공에 따른 활성 증진효과를 알아보기 위해 볶음 처리하였다. 볶음 처리한 참외 종자는 볶음 처리하지 않은 종자보다 활성이 2~4배까지 증가하는 경향을 보여주었다. 추출용매에 따른 활성은 에탄올 추출물, 헥산 추출물, 물 추출물 순으로 항암활성이 나타났다. 인체 유래 5종(MCF-7, A549, AGS, HT-29, HepG2) 암 세포주를 이용하여 항암 활성의 조직 특이성을 알아보고자 하였다. 참외 볶음 종자 에탄올 추출물이 간암 세포주인 HepG2세포와 유방암 세포주인 MCF-7 세포에서 우수한 항암활성을 보여주었다. 용매분획법을 실시하여 제조한 분획물의 경우 에탄올 추출물보다 활성이 증가하였고, 비극성 분획물인 에칠아세테이트층이 극성 분획물인 부탄올층 보다 강한 항암활성을 보여주었다. 이상의 연구결과, 참외 볶음종자가 간암과 유방암 예방 및 치료 소재로서 개발될 가치가 있는 것으로 사료된다.

This study was performed to determined the antioxidant activities, anticancer and immuno-activities of anthocyanin fraction from Rubus coreanus Miquel fruits (Bokbunja). Anthocyanin fraction extracted from Bokbunja revealed the presence of three anthocyanin components, which were tentatively identified as cyanidin 3-O-sambubioside, cyanidin 3-O-xylosylrutinoside and cyanidin 3-O-rutinoside using RP-HPLC/DAD/MS. The anthocyanin fraction from Bokbunja always showed reducing power and high scavenging activities against DPPH, hydroxy radical (OH) and superoxide anion radical (O2-) similar to general synthetic antioxidant and polyphenol compounds from plant origin. Anthocyanin fraction from Bokbunja showed high inhibition on proliferation of LNCaP and A549 cells and did not inhibit the proliferation of other cancer cells. Immuno-activities of Anthocyanin fraction from Bokbunja were investigated, it showed high promotion of human B and T cells growth about 50% and secretion of IL-6 and TNF-α by treatment after 6 days. Over all, the result of the study suggest that anthocyanin fraction from Bokbunja displays antioxidant activity comparable to that general synthetic antioxidant, also, anthocyanin fraction from Bokbunja are expected to be good candidate for development into source of anticaner and immuno-activator agent in food industry.

종피색이 다른 세 품종을 이용하여 총페놀함량, 항산화활성 및 항암활성의 변이를 조사하였다. 총페놀함량은 흑진주벼의 쌀겨와 영이 적진주벼와 일품벼보다 높게 나타났으며, 흑진주에서는 쌀겨가 영보다 함량이 높았으나 다른 두 품종은 영이 쌀겨보다 함량이 높았다. DPPH 자유기 소거능은 흑진주와 적진주의 활성이 일품벼 보다 높았으며, 쌀겨 추출물이 영 추출물보다 훨씬 높은 활성을 보였다. 환원력은 흑진주의 쌀겨 추출물이 다른 품종의 쌀겨 추출물보다 3~16배의

This study was performed to enhance anticancer activities of Lithospermum erythrorhizon by eluting high amount of shikonin through ultra high pressure process. Extraction yield was increased up to 5~10% by ultra high pressure process, compare to the normal extraction processes such as water solvent extraction, 70% ethyl alcohol solvent extraction. The cytotoxicity of the extracts (1.0μg/ml) from ultra high pressure process was showed the lowest cytotoxicity 13.4% for human lung cell (HEL299). The anticancer activities showed 80~85% by adding 1.0μg/ml of the extracts from ultra high pressure process in several cancer cell lines such as AGS, Hep3B, MCF-7 and HeLa cells. Among them, MCF-7 cell of the endocrine system was highest inhibited than other cells. The anticancer activities of the extracts from ultra high pressure extraction process showed 10~15%, which was higher than the extracts from normal extraction processes. From HPLC analysis of the extracts, the contents of shikonin in the extracts from ultra high pressure process was 11.42% (w/w), which was 20% higher than others. This results indicate that ultra high pressure process could increase the extraction yield of shikonin and other contents, which resulted in higher anticancer activities.