Human bitter taste-sensing type 2 receptors (hTAS2Rs) are expressed in various human tissues and may be associated with various cell signaling pathways, cell progression, and cell physiology in each tissue. hTAS2Rs can be a potential drug target because it is also expressed in some cancer cells. Xanthorrhizol (XNT) has various biological activities, such as anticancer, antimicrobial, anti-inflammatory, and antioxidant. XNT produces a bitter taste, but the specific hTAS2R activated is unknown, and the hTAS2R-mediated effect of XNT on cancer cells has not been studied. This study discovered the target receptor of XNT among 25 hTAS2Rs and confirmed the possibility of the hTAS2R-mediated inhibition of cancer cell proliferation. XNT activated only one receptor, hTAS2R38 (EC50=1.606±0.021 g/mL), and its activity was inhibited by probenecid, a hTAS2R38 antagonist. When HepG2 and MCF-7 cells were treated with XNT or phenylthiocarbamide (PTC), a known hTAS2R38 agonist, both chemicals inhibited cancer cell proliferation. XNT targets the human bitter taste receptor TAS2R38 and inhibits the proliferation of HepG2 and MCF-7 cells mediated by TAS2R38. This suggests that TAS2R38 may be a new target for disease treatment and a potential new factor for drug development.

The objective of this study was to investigate the anticancer effects of EMPS (edible mushroom mycelium polysaccharide: Tremella fuciformis) in animal models with colorectal cancer induced by AOM/DSS. The experimental groups consisted of Nor (normal), NC (AOM/DSS), EMPS (EMPS 50, EMPS 100), and PC (Fluorouracil). The NC group had the highest number of colon tumors, whereas it was observed that tumor occurrence was significantly reduced in the EMPS consumption group. The expression of Bcl-2, an apoptosis inhibitor, was significantly lower in the EMPS 50 & 100 and PC groups. On the other hand, the mRNA gene expression of Bax, a factor that induces apoptosis, was significantly higher in the EMPS 50 & 100 and PC groups compared to the NC group. The mRNA expression levels of TNF-α and COX-2 significantly increased in the NC group, but showed a significant decrease in the EMPS and PC groups, indicating inhibition of the cancer-promoting response of cells. At the phylum level of the mice's intestinal microbial composition, the proportion of Bacteroidetes tended to decrease, while the proportion of Firmicutes tended to increase with EMPS administration. This suggests that changes in the gut microbiota caused by inflammation can be influenced by dietary intake.

Comparing the quality characteristics of kimchi were measured and anticancer effects using AGS human gastric cancer cells were observed. Five kinds of kimchi samples were made of Kanghwa Baek kimchi (KB), Kangwha Turnip kimchi (KT), Turnip: Chinese cabbage = 1:1 Baek kimchi (T1B1), Turnip:Chinese cabbage = 4:1 Baek kimchi (T4B1), Turnip mul kimchi (T). As a result T kimchi showed the best fermentation characteristics among the five samples. T kimchi had a lower percentage of the total number of aerobic bacteria, while the number of lactobacillus was higher than that of other samples. The mRNA and protein expression levels of apoptosis-related factors found that T kimchi significantly increases the mRNA expression levels of caspases-3 and caspases-9 in AGS human gastric cancer cells as compared to the other kimchi samples. It showed high anticancer effects in the order of T, T1B1, and KB kimchi. As the anticancer effect of Turnip mul kimchi made only of turnip was higher, the higher the turnip content, the higher the anticancer effect. These results show that there were changes in fermentation characteristics such as pH, acidity, number of lactic acid bacteria, and anticancer effects according to the ratio of turnip and cabbage.

Spirodelae Herba (SH) and Perilla Frutescens (PF) extracts have been widely used in clinical practice with various disorders for thousands of years. There are some reports regarding the anticancer effects of SH and PF each by each, but their mixture have not been investigated and their mechanisms also have not been clear. The purpose of the present study was to investigate the anticancer mechanisms and their effects of the mixture of SH and PF extracts on head and neck cancer cell line. Head and neck carcinoma KB cells were treated with SH, PF and their mixture. Anticancer effects were investigated by searching cancer cell death pathway; apoptosis and autophagy, which have been regarded to be effective and safe methods. Apoptosis, which is termed a programmed cell death, was observed by TUNNEL assay. Autophagy, which is termed a type II programmed cell death, was observed by acridine orange red staining. Additionally, the protein expressions associated with apoptosis and autophagy were detected for their mechanism by western blots. The mixture of SH and PF extracts induced autophagic and apoptotic cell death simultaneously in cancer cells. And 0.4 mg/ml of the mixture with SH and PF extracts down-regulated the expression of mTOR, however, the expressions of ATG5 and LC3-II, which induced autophagy, up-regulated. The mixture of SH and PF extracts also down-regulated the expressions of Bcl-2, but up-regulate the expressions of PARP-1 cleavage, Caspase-9 cleavage, Caspase-3 cleavage and BAX, which induced apoptosis. Taken together, these results suggested that the mixture of SH and PF extracts induce autophagic and apoptotic cell death simultaneously in head and neck cancer cells and it could be used as an alternative for anti-cancer drugs.

Lindera glauca Blume has been used in Korean traditional medicine to treat the symptoms of paralysis, abdominal pain, speech disorders, extravasations, contusions, and pain caused by rheumatoid arthritis. We investigated the effect of L. glauca Blume extracts on the proliferation of colorectal cancer cells in vitro using HCT116 human colorectal cancer cell lines. We also investigated its mechanism of action. For this purpose, we used the MTT assay, western blotting, DNA fragmentation analysis, and flow cytometry. HCT116 cells were cultured in several concentrations of ethanol extracts of L. glauca Blume root (0, 50, 100 μg/mL). In this study, colon cancer cell growth was inhibited by L. glauca Blume root extract in a dose-dependent manner. It was associated with induction of apoptosis as assessed by nuclear fragmentation and cell cycle analysis. Apoptosis was assessed using western blotting for TNF-α, IL-6, NF-κB, Caspase-3, PARP, Bax, Bcl-2, and SIRT1. The extract also dose-dependently upregulated the expression Bax, the pro-apoptotic gene and downregulated the expression of the anti-apoptotic gene Bcl-2. Furthermore, the extract enhanced Caspase-3 activity in a dose-dependent manner. Our findings provide evidence that L. glauca Blume extract may mediate its anti-proliferative effect via the modulation of apoptosis.

Fenbendazole (FBZ) is one of the safest anthelmintic drugs. FBZ has been found to have anti-cancer effects by destabilizing microtubules. In this study, a synergistic effect of paclitaxel (PA), a microtubule-stabilizing anti-cancer agent, and FBZ was investigated on HL-60 cells, a human leukemia cell line. The metabolic activity of cells significantly decreased and the nucleus morphology upon the treatment of FBZ and PA based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and Hoechst 33342 staining, respectively. To investigate the involvement of reactive oxygen species (ROS), the metabolic activity of the cells after treatment of N-acetyl-L-cysteine (NAC) was measured. Indeed, NAC significantly increased the metabolic activity of the cells treated with FBZ and PA, suggesting that both drugs affect at least in part via ROS. Furthermore, FBZ and PA increased cell death in an annexin V- fluorescein isothiocyanate/propidium iodide staining assay. Taken together, FBZ and PA have a synergistic anti-cancer activity on HL-60 cells at a certain concentration. These results may provide researchers and clinicians in cancer-related fields with some valuable information to broaden the use of FBZ.

The study was conducted to identify the anti-inflammatory and anti-cancer effects in sprouts of mouse-eyed bean (Rhynchosia nulubilis), ginseng (Panax ginseng), perilla (Perilla frutescens), broccoli (Brassica oleracea var. italica), and lettuce (Lactuca sativa) grown with organic germanium concentrate. Western blot analysis was performed to assess the antiinflammatory activity of the extract. All extracts exhibited noticeable anti-oxidant activity, indicating a significant correlation between the germanium content and anti-oxidant activity (p<0.05). In particular, rat-eyed bean sprouts with the highest germanium content showed significant anti-inflammatory activity (p<0.05) by significantly inhibiting the expression of the inflammatory complexes, NLRP3, cytokines IL-1β and caspase-1. Ginseng and broccoli sprouts showed strong anti-cancer properties and had high anti-oxidant effects (p<0.001). Germanium-concentrated water allows the mass production of agricultural products containing high concentrations of organic germanium. Agricultural produce grown with germanium concentrate add organic germanium to various physiological active ingredients, increasing the anti-oxidant and anti-cancer effects. These results strongly suggest that agricultural products containing high germanium concentrations can be used as novel health supplements to improve health.

Doenjang is a major fermented soy-based food in Korea. Recent investigations have shown that fermented soybean foods have immunity-enhancing, anti-cancer, anti-obesity and anti-diabetic effects. Several studies also have reported that genistein and daidzein, which are easily absorbed in the body are produced in larger quantities in aged doenjang. The purpose of this study was to evaluate the variations in the anti-cancer effects of commercialized doenjang as it ages. Four groups were formed for this study according to aging periods of doenjang, namely short (under 5 years, S group), mid (under 10 years, M group), long (under 15 years, L group) and very long (over 15 years, E group). The anti-cancer effects of doenjang were determined by cell cytotoxicity assays in A549, YAC-1, and HepG2 cancer cell lines. Also, NK cell activity and splenocyte proliferation were assayed for cancer immunotherapy. The quantities of phenolic compounds in doenjang at different ages were also measured. The results showed that the anti-cancer effects increased in the S and M groups for all three cancer cell lines. Interestingly, similar to this result, splenocyte proliferation and NK activity were also the highest in the S and M groups. In contrast, the E group showed significantly reduced splenocyte proliferation. The quantity of phenolic compounds was similar to that of the anti-cancer results. Collectively, these results suggest that the fermentation period of doenjang plays a very important role in determining its anti-cancer effects.

L-carnitine은 라이신과 메티오닌으로 생합성되며 골격근 과 심근을 포함한 다양한 동물조직에서 발견된다. L-carnitine이 포함된 식품으로는 양고기, 소고기, 돼지고기 등이 있고 근육발달에 도움을 주며 뼈를 강화하거나 대사작용을 도와주는 기능을 하여 영양 보조제로 많이 섭취하는 것으로 알려져 있다. 최근 L-carnitine은 제 2형 당뇨병, 골다 공증, 대사성 신경증후군 등의 다양한 질병의 약물로도 연구 되고 있으며 암에서는 치료 보조제로 개발되어있다. 하지만 대장암에서의 L-carnitine에 대한 효과 및 기전에 대해서는 명확하지 않고 연구된 바가 없기 때문에 본 연구에서 저자들은 L-carnitine의 효능을 인간대장암세포주 HCT116에서 규명하고자 하였다. L-carnitine은 세포 내 활성산소종 (ROS)를 높은 수준으로 증가시켜 세포 증식을 억제하였다. 또한, 세포 증식과 죽음에 관련한 단백질 ERK1/2와 p38을 유의적으로 활성화 시킨다는 것을 입증 하였다. 이때, ERK1/2 억제제(PD98059)를 처치하여 ERK1/ 2의 활성화가 활성산소종 발생 및 세포사멸에 중요하다는 것을 밝혔다. 따라서, 본 연구 결과는 L-carnitine이 대장 암세포주의 증식을 억제 할 수 있고 이는 대장암의 치료에 있어 잠재적인 치료 물질이 될 수 있음을 시사하며 이 과정에 관여하는 신호전달기전을 조사하여 항암의 치료기 전에서 활성산소종이나 ERK1/2, p38 단백질의 활성화의 중요성을 제시하였다.

우르솔릭산은 항암, 항산화, 항염증 작용과 같은 다양한 효과를 지니고 있다. 본 연구에서는 우르솔릭산이 인간 흑색종 암세포인 A375SM과 A375P 세포에 항암효과가 있는지 확인하였다. 두 세포의 생존율은 MTT assay를 통하여 확인하였으며 증식률은 Wound healing assay로 확인하 였다. 두 세포의 apoptotic body와 apoptosis 비율의 확인을 위한 DAPI 염색과 유세포 분석을 진행하였다. 그리고 웨스턴 블로팅을 통하여 흑색종 세포의 우르솔릭산의 농도에 따른 apoptosis 단백질의 유도를 조사하였다. 우르솔 릭산의 처리 농도에 따라 흑색종 세포의 생존율 감소와 증식률 감소를 확인하였다. DAPI 염색을 통하여 우르솔 릭산의 농도가 증가함에 따라 흑색종 세포의 염색체 응축 이 농도 의존적으로 증가하였고, 유세포 분석을 통하여 우르솔릭산에 대하여 농도 의존적으로 흑색종 세포의 apoptosis 비율의 증가를 확인하였다. 그리고 웨스턴 블로팅을 통해 흑색종 세포 A375SM과 A375P의 우르솔릭산 12 μM 농도에서 cleaved-PARP와 Bax의 증가와 Bcl-2의 감소를 확 인하였다. 본 연구는 우르솔릭산의 농도를 0 에서 20 μM 수준의 저농도에서 진행하였으며, 물질 처리 후 24 시간 뒤 결과를 가지고 분석하였다. 본 연구의 결과로 보아 우르솔릭산은 흑색종 세포 A375SM과 A375P에서 apoptosis 관련 단백질들의 조절을 통해 항암효과를 일으키는 것으로 사료된다.

Purpose: The objective of this study was conducted to investigate the effects of rutin, buckwheat components on cell growth and anti-inflammation in adipocyte 3T3-L1 and human colon cancer cell SW-480. Methods: We cultured 3T3-L1 adipocyte and SW-480 colon cancer cell to confluence, at which time starvation was induced with SFM for 1 day. Cells were then cultured in medium containing 0, 25, 50, or 100 μmol/mL of rutin 3T3-L1 or 0, 10, 20, or 40 μmol/mL SW-480. Cell viability was measured using a cell viability kit. In addition, we examined the expression of mRNA related to inflammation. RT-PCR was used to quantity tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) mRNA levels. Results: Rutin significantly inhibited 3T3-L1 and SW-480 cell proliferation in a dose and time dependent manner. Rutin also significantly reduced the mRNA expression of IL-1β, IL-6 and TNF-α at the highest dose. In addition, rutin treatment caused a significant reduction in COX-2 and iNOS mRNA levels compared to the control group. Conclusion: Overall, our results suggest that rutin has the potential to reduce inflammation, and that these effects are greater during tissue-damaging inflammatory conditions.

시스플라틴은 지난 몇 십년간 가장 많이 사용되고 있는 항암제 중 하나이다. 2가의 시스플라틴의 가장 큰 단점은 암세포 뿐만 아니라 정상세포도 공격하여 부작용을 나타낸다. 본 연구에서는 이러한 단점을 줄이기 위해 목표로 한 타겟을 공격하여 빠른 시간 내에 암세포를 죽일 수 있는 4가의 백금화합물 3과 4를 합성하였다. 합성된 Pt(IV)-Bu2 3 and Pt(IV)-Val2 4는 NMR과 질량분석기를 통하여 구조를 확인 하였다. 합성된 Pt(IV) 화합물 3과 4는 위암세포주인 MCF-7을 대상으로 한 MTT assay를 통해 항암효과를 조사하였다. 그 결과 시스플라틴은 39%, Pt(IV)-Bu2 3와 Pt(IV-Val2 4는 50μM 농도에서 각각 54%와 84%의 세포사멸을 보였다.

Vegetable soup has been reported to have anti-inflammatory, anti-oxidative and anti-cancer effects. In this study, five kinds of vegetable soup were developed using a new manufacturing process and compositional changes in raw material, and anti-cancer and immuno-stimulatory activities were evaluated. Cytotoxicity tests based on MTT assay revealed that all vegetable soups had strong inhibitory effects against CT26 mouse colon cancer cells, with soups including Solomon’s seal being most effective based on comparison of IC50 values. Apoptosis in response to vegetable soup was occurred by 3-5 fold on cancer cells compared to normal cells. Mouse splenocytes increased by 266-541% in response to addition of vegetable soup in an in vitro proliferation experiment. In co-culture with splenocytes and CT26 cancer cells, splenocytes increased by more than 280% in every vegetable soup treatment, while cancer cells decreased by about 60% and cytokines such as IFN-γ and IL-12 were secreted from splenocytes in high levels only in response to vegetable soup including Solomon’s seal. In conclusion, all vegetable soups developed in this study had anti-cancer effects, and vegetable soup including Solomon’s seal showed the strongest anti-cancer and immuno-stimulatory effects. These results suggest that functionality of vegetable soup could be increased by changes in manufacturing processes and raw materials composition.

Human malignant melanoma is an aggressive skin cancer which has been rising at a greater rate than any other cancers. Although various new therapeutic methods have been developed in previous studies, this disease has properties of high proliferation and metastasis rate which remain obstacles that have lead to a poor prognosis in patients. It has been reported that a specific Lactobacillus extract has anti-cancer and –metastasis effect in vitro and in vivo. However, previous research has not specified precisely what effect the Lactobacillus rhamnosus GG (LGG) extract has had on human malignant melanomas. In this study, we showed that the LGG extract has anti-cancer and –metastasis effects on the human malignant melanoma cell lines, A375P and A375SM. At first, it was found that, while the LGG extract affects human neonatal dermal fibroblasts slightly, it induced the dose-dependent anti-cancer effect on A375P and A375SM by a WST-1 proliferation assay. As a result of a real-time PCR analysis, the expression patterns of several genes related to cell cycle, proliferation, and apoptosis were modulating in a manner that inhibited the growth of both malignant melanoma cell lines after the treatment of the LGG extract. Furthermore, genes related to the epithelialmesenchymal transition were down-regulated, and migration rates were also decreased significantly by the LGG extract. Our study showed that the LGG extract could be used as a potential therapeutic source.

Fludarabine, a chain terminating anti-cancer drug, is a purine analogue that causes DNA strand breaks in normal cells. In this study, we determined if A. melanocarpa and Korean red ginseng extract mixture reduce cytotoxicity of fludarabine. Treatment of HaCaT cells with 10 μM of fludarabine for 24 hours decreased cell viability and increased DNA strand breaks. Treatment of A. melanocarpa and Korean red ginseng extract mixture for 24 hours increased cell viability as compared with single extract treatment. The protective effect of these extracts on cell activity increased in a concentration-dependent manner. DNA strand breaks induced by fludarabine decreased as concentration of extract mixture increased. p-H2AX level, a marker of DNA strand breakage, decreased depending on the concentration of extract mixture. The effect of mixed extract of A. melanocarpa and Korean red ginseng on DNA damage is due to the anti-oxidative effect of A. melanocarpa and signal transmission through glucocorticoid receptor upon binding of saponin of Korean red ginseng.

Recently, the area of marine resources has become concerned with sources for the next generation of the bio-industry. Until present, development of the marine resources has remained limited, although a large number of these resources are considered to have potential for various significant biological activities. Most marine sponges, marine algae and coral could be used to create specific compounds for survival against a harsh environment. Therefore, it was necessary that these materials needed to be elucidated with biological activities, such as like anti-inflammatory, anti-viral or anti-cancer effects for their utilization in the bio-industry. In this study, we screened extracts of marine resources for their anti-cancer effect on human colorectal cancer cells. These resources were collected at Kosrae of Micronesia on April, 2013 and extracted with methanol. Cytotoxicity of marine resources was observed. Of a total of 20 specimens, three specimens dose-dependently demonstration inhibition of cell viability. Furthermore, cells treated with these specimens for 48h were induced p53, p21, Bax and caspase-3. The results suggest that they involved p53-mediated apoptosis. Two positive specimens (1304KO-327 and 1304KO-329) were verified as the identical materials, which are Hyrtios sp. Unfortunately 1304KO-207 was not yet classified and needed to identify in the further study. There results suggested that marine resources with positive potential in anticancer effect would be good candidates as useful bio-resources.

Anthricin (Deoxypodophyllotoxin), a naturally occurring flavolignan, has well known anti-cancer properties in several cancer cells, such as prostate cancer, cervical carcinoma and pancreatic cancer. However, the effects of Anthricin are currently unknown in oral cancer. We examined the anticancer effect and mechanism of action of Anthricin in human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that Anthricin inhibits cell viability in a dose- and time-dependent manner (IC50 50 nM) in the MTT assay and Live & Dead assay. In addition, Anthricin treated FaDu cells showed marked apoptosis by DAPI stain and FACS. Furthermore, Anthricin activates anti-apoptotic factors such as caspase-3, -9 and poly (ADP-ribose) polymerase (PARP), suggesting that caspase-mediated pathways are involved in Anthricin- induced apoptosis. Anthricin treatment also leads to accumulation of the pro-apoptotic factor Bax, followed by inhibition of cell growth. Taken together, these results indicate that Anthricn-induced cell death of human FaDu hypopharyngeal squamous carcinoma cells is mediated by mitochondrial-dependent apoptotic pathway. In summary, our findings provide a framework for further exploration on Anthricin as a novel chemotherapeutic drug for human oral cancer.

해양생물을 포함한 천연물질은 신약개발의 원천 소재로서 매력적이며, 특히 무수한 미지의 해양생물들의 연구가 관심을 받고 있다. 기존의 연구에서 미크로네시아에서 채취한 해면동물 40여종에 대하여 항증식 효과를 다양한 암세포주에서 검색한 바 있다. 본 연구에서는 그 중 Cos-cinoderma sp.의 작용 및 그 기전을 살펴보았다. 특히, 암억제유전자 p53의 발현을 억제시킨 세포주(HCT116 p53KO 과 RKO-E6)에서의 차이점을 비교하였다. 세포생존률 시험에서 Coscinoderma sp. 추출물은 p53의 유무와 상관없이 암세포의 증식을 억제하였음을 확인하였다. 이 암세포증식 억제 효과가 p53 존재에 따라 다르게 나타나는지 알아보기 위하여 세포사멸 관련 단백질 발현양을 Coscinoderma sp. 처리한 각 세포주에서 비교하였다. 그 결과, Coscinoderma sp.를 HCT16 세포주에 처리하였을 때, p53과 Noxa의 발현이 증가하는 것을 관찰하였고, caspase-9이 분절되면서 감소하는 것으로부터 apoptosis를 일으킨다고 여겨진다. 반면, p53이 결핍된 HCT116세포주에서는 Coscinoderma sp. 에 의하여 p21과 mTOR의 발현이 증가되는 것을 확인하였고, 이는 senescence를 야기할 수 있다고 여겨진다. 본 연구로부터 Coscinoderma sp.는 p53의 존재여부에 따라 상이한 작용기전을 매개하여 대장암 세포주의 증식을 억제한다는 것을 알 수 있었다. 이는 새로운 항암제의 개발 가능성을 제시하는 것으로, Coscinoderma sp.의 활성 성분에 대한 지속적인 연구가 이루어 져야 할 것으로 보인다.