Ophiopogonin D (OPD) is a steroidal glycoside derived from Ophiopogon japonicus , a traditional Chinese medicine with diverse biological activities, including antithrombosis, anti-inflammation, and antitussive effects. To investigate the cellular effects and mechanisms of OPD on oral squamous cell carcinoma, cell viability was explored, and the effects of OPD on cell cycle regulators, apoptotic marker proteins, and key proteins involved in metastasis and signaling pathways were examined by MTT assay and Western blotting in YD38 cells. OPD strongly inhibited cell proliferation and induced caspase-dependent apoptosis of YD38 cells by suppressing the cell cycle and activating caspase-3 and poly ADP ribose polymerase. Additionally, OPD suppressed the expression of vital proteins regulating metastasis and proliferation within the integrin/matrix metalloproteinases/FAK and AKT/PI3K/mTor pathways. Thus, OPD can be a potential treatment candidate for gingival cancer.
In this study, we investigated the antioxidant activity and anticancer effect of Coprinus comatus (C. comatus) extracts. Free radical scavenging capacity of the C. comatus extracts was evaluated in vitro by the DPPH assay. C. comatus exhibited the strong DPPH radical scavenging activity. In vitro tests were also performed to examine the anticancer activity of C. comatus against 293 human normal epithelial kidney cells and various human cancer cell lines including AGS, Hela and HCT-15. C. comatus extracts showed the potent cancer cell-selective growth inhibitory activity against AGS, Hela, and HCT-15 cells, but slightly inhibited 293 normal cell growth. We examined several biological activities such as antitumor effects of C. comatus extracts in vivo. Solid tumors were induced by Sarcoma-180 inoculation in the left groin of BALB/c mice and then C. comatus extracts were oral administered. After 5 weeks, all mice were sacrificed and their tumor weights were measured. C. comatus extracts exhibited the most effective antitumor activity, and the tumor growth rate was inhibited by 55% in comparison with control group. Taken together, these results indicate that C. comatus extracts showed high antioxidant activity and possessed powerful antitumor activity.
The antitumor effects of octyl gallate (OG) were investigated on FaDu human hypopharyngeal squamous carcinoma cells. At various concentrations, OG inhibited the proliferation of FaDu cells by suppressing cell cycle regulators and induced apoptosis by activating caspase 3 and its downstream poly (ADP-ribose) polymerase, thereby damaging DNA. Immunoblotting demonstrated that OG significantly suppressed the expression of integrin family proteins (integrin α4, αv, β3, β4), hindering cell adhesion. The reduced expression of integrins subsequently mediated the mitogenactivated protein kinase signaling pathway to stimulate the activation of extracellular signal-regulated kinases and c-jun N-terminal kinases, leading to apoptosis. Thus, OG demonstrated antitumor activity on hypopharyngeal squamous carcinoma cells by suppressing cell proliferation and inducing apoptosis.
The antioxidant and antitumor properties of natural products, often recognized in traditional medicine systems, represent therapeutic modalities to reduce or prevent uncontrolled oxidation processes which in turn potentially ameliorate or tumor based symptoms of chronic diseases. We have studied the antioxidant and antitumor effects of Amanita muscaria (A. muscaria) in vitro and examined whether the A. muscaria has synergistic effects on antioxidant and antitumor properties. Although A. muscaria induced a dose-dependent increase in antioxidant activity, the latter has a consistently higher antioxidant effect. In mouse monocytes, the lipopolysaccharide- (LPS-) induced tumor necrosis- (TNF-) synthesis was significantly inhibited by A. muscaria in a dose dependent manner and synergistic effects were clearly demonstrated with the A. muscaria on TNF- inhibition. A. muscaria effect was also evident on inhibition of nuclear factor-kappa B activity, cyclooxygenase-II activity, and lipid peroxidation in mouse monocytes. This presented results may be a starting point for a comprehensive characterization of biological effects of A. muscaria.
The present study is designed to explore an anti-tumor activity on crude extracts of Oplopanax elatus. Water extractions of Oplopanax elatus were performed at 100℃(OeE-100). OeE-100 doses up to 62.5 ㎍/㎖ had no cytotoxicity on the tumor cell lines in vitro. In experimental lung metastasis of colon26-M3.1 carcinoma or B16-BL6 melanoma, the prophylactic intravenous (4~100 ㎍/mouse) or oral (2 ㎎/mouse) administration of OeE-100 significantly inhibited tumor metastasis as compared with tumor controls. Peritoneal macrophages stimulated with OeE-100 produced various cytokines such as TNF-α, IL-6 and IL-12. In an analysis of NK-cell activities, i.v. administration of OeE-100 (10~100 ㎍/mouse) significantly augmented the cytotoxicity to YAC-1 tumor cells. Vaccination of mice with boiling-treated tumor cells (BT-vaccine) in combination with OeE-100 (100 ㎍/mouse) showed higher inhibitions in tumor metastasis when compared with the mice of BT-vaccine treatment. In addition, the splenocytes from OeE-100 admixed BT-vaccine immunized mice secreted a higher concentration of Th1 type cytokine such as IFN-γ. These results suggested that the OeE-100 stimulated immune system and was a good candidate adjuvant of anti-tumor immune responses.
To evaluate the antioxidant and potential of Humulus japonicus, total polyphenol and flavonoid content, radical scavenging activities, and antitumor activities were measured. The total polyphenol and flavonoid contents of the methanol extracts from Humulus japonicus were 30.13±1.13 and 13.61±0.49 ㎎ gallic acid equivalent/g extract, respectively. DPPH radical and hydroxyl radical scavenging activities of methanol extracts of Humulus japonicus were 60% and 35%, respectively. The Humulus japonicus higher activities of anticancer activities on liver cancer cell lines compared to other cancer cell lines.
The aim of this study was to investigate the antitumor activity of solvent fractions from Auricularia auricula-judae 70% ethanol extract and confirmed the active components of dichloromethane fraction showing a potent antitumor activity than other fractions in the broncheoalveolar and gastric cancer cells. The solvent fractions of Auricularia auricula-judae extract, inhibited the growth proliferation of tumor cells in dose-dependent manner. The principle components of dichloromethane fraction were 5,11,17,23-tetrakis (1,1-dimethyl)-28-methoxypentacyclo [19.3.1.1 (3,7).1 (… (65.85%) and diazane (6.17%). The antitumor active components, diazane and gibberellic acid (GA3) were identified in this fraction by GC-MS analysis and lower antitumor activities than dichloromethane fraction. The unknown components of dichloromethane fraction were responsible for its cytotoxic effects on tumor cells. Based on IC50 value, gibberellic acid was little cytotoxic itself. According to PCR amplification, the apoptosis of tumor cells were induced by the down-regulation of Bcl-2 and over-expression of P53 on the presence of solvent fractions, diazane and gibberellic acid. Thus, these findings suggest that the dichloromethane might be used as functional feed additive that suppress the tumor growth in the body than other solvent fractions of Auricularia auricula-judae extracts.
Auricularia auricula-judae has long been used as food and traditional remedies in Asian countries such as Korea and China. In this study, we evaluated the in vitro anti-tumor activity of various fractions from the ethanol extracts of Auricularia auricula-judae using various tumor cell lines. To do this, the mesh of Auricularia auricula-judae was mixed with 70% ethanol and heated at 1000C for 6 hrs and ethanol extract (ETOH) was collected. Ethanol extract was fractionated with dichloromethane (DCM), ethyl acetate, n-butanol and a water extract at room temperature as well as concentrated in a vacuum concentrator at a controlled temperature(<500C). The P388D1 macrophage and Sarcoma 180, human NSCLC NCI H358 (bronchioalveolar) and SNU1 cells (Gastric carcinoma) were cultured in RPMI. As the results, the cytotoxicity of the fractional extracts decreased significantly (P<0.05) in a dose-dependent manner. Dichloromethane extract (1 mg/ml) was the highest (P<0.05) in all experimental cell lines. There was also a significantly different sensitivity (P<0.05) among the P388D1, Sarcoma 180, NCI H358 and SNU1 cells for the fractional extracts. According to IC50 values, the most potent cytotoxic activity of dichloromethane fraction was found in Sarcoma 180 and NCI H358 cell lines. Butanol fraction appeared more cytotoxic to SNU1 cell line and water fraction had the highest cytotoxicity in P388D1 cell line. We did not find any significant difference between MTT and SRB assays in their ability to estimate cytotoxicity in all cell lines. Our findings suggest a potent antitumor activity of various fractions from the ethanol extracts of Auricularia auricula-judae depending on the solvent fractions and tumor cell lines. Further in vitro and in vivo studies will provide more information on the active compounds responsible for these activities and their potential as an anti-cancer remedy.
선학초 메탄올 추출물을 유기용매를 이용하여 분획하고 각각의 분획별 항산화 및 항암 활성을 조사하였다. 항산화 활성으로 총페놀, 전자공여능, 아질산염 소거능을, 효소 저해 활성으로 XOase 저해 활성을 조사하였으며, 암세포인 HT-29, SNU-1, HeLa 세포에 대한 성장 저해 활성을 조사하여 기능성 식품으로의 개발 가능성을 알아보고자 하였다. 총 페놀 함량은 EtOAC와 BuOH 분획에서 39.89%, 39.56%로 가장 높았고, 전자공여능 또한 EtOAC 분획에서 92.90% (500 μg/ml), 94.47% (1000 μg/ml), BuOH 분획에서 93.77% (500 μg/ml), 92.90% (1000 μg/ml)로 90% 이상이었다. 아질산염 소거능도 1000 μg/ml의 농도에서 50% 이상이었으며, XOase 저해활성은 93.06% (EtOAC) 와 91.73% (BuOH)로 높은 활성을 보였다. 암세포 성장 저해활성을 측정한 결과 hexane 분획에서 가장 높았고 HT-29에 대해 11.63%-90.07%, SNU-1에 대해 16.84%-95.11%, HeLa에 대해 4.44%-96.40%였다. 이상의 결과에서 선학초의 EtOAc, BuOH 분획물은 항산화 활성이 있는 기능성 식품으로의 개발이 가능할 것으로 생각되며, hexane, chloroform 분획은 위암, 대장암과 자궁경부암 치료보조제로서의 개발을 위한 추가적인 연구가 필요하다고 생각된다.
송이가 발생되지 않는 것으로 알려져 있는 경기지역의 과거 송이발생지와 발생가능지역을 중심으로 ’99∼’00년간 송이 발생현황 및 식생조사를 실시한 결과를 요약하면 다음과 같다 1. 도내 송이발생 지역은 조사지역 19개 지역중 여주군 강천면 걸은리 등 16개 지역이었고 년간 발생량은 총470∼600kg정도였으며, 여주군 강천면 걸은리, 북내면 도전리와 포천군 영중면 금주리 등 일부지역은 현재까지 양호한 식생환경조건을 유지하고 있었으나, 향후 지속적인 적송림의 유지관리가 요구되었으며, 나머지 지역에서는 식생변화 등으로 송이발생량이 대폭 감소하였거나 발생되지 않았다. 2. 도내 조사지역의 송이버섯은 9월 12∼15일에 발생되기 시작하여 9월말에 최성기, 10월 7∼9일경 마무리 되었고 송이발생전후의 기온과 지온은 9월 5∼7일경에 송이자실체 발생을 위해 자극을 받기 시작하는 온도인 19℃ 이하로 낮아졌고, 그 후 약 5∼7일 이후에 송이자실체가 발생되었으며, 송이발생기간동안 기온은 12∼18℃, 지온은 14∼18℃를 유지하였다. 3. 송이 발생지점의 적송밀도는 100㎡당 5.1∼27.1그루, 수령은 15∼50년생, 수고는 4∼11m이었고, 활엽수 및 관목의 밀도가 43∼80%로 높아 간벌과 적송의 관리가 시급한 것으로 조사되었다. 4. 유기물층의 깊이는 여주, 포천지역은 3.5∼4.5㎝, 양평, 가평, 광주는 7.2∼7.7㎝였으며 울폐도는 50∼75%범위였다. 5. 토성은 조사지역 모두 사질토였고 토양pH는 4.3∼5.1, 유기물함량은 3.91∼8.28 범위였다.
Metformin is the most commonly prescribed anti-diabetic drug with relatively minor side effect. Substantial evidence has suggested that metformin is associated with decreased cancer risk and anticancer activity against diverse cancer cells. The tyrosine kinase inhibitor imatinib has shown powerful activity for treatment of chronic myeloid leukemia and also induces growth arrest and apoptosis in colorectal cancer cells. In this study, we tested the combination of imatinib and metformin against HCT15 colorectal cancer cells for effects on cell viability, cell cycle and autophagy. Our data show that metformin synergistically enhances the imatinib cytotoxicity in HCT15 cells as indicated by combination and drug reduction indices. We also demonstrate that the combination causes synergistic down-regulation of pERK, cell cycle arrest in S and G2/M phases via reduction of cyclin B1 level. Moreover, the combination resulted in autophagy induction as revealed by increased acidic vesicular organelles and cleaved form of LC3-II. Inhibition of autophagic process by chloroquine led to decreased cell viability, suggesting that induction of autophagy seems to play a cell protective role that may act against anticancer effects. In conclusion, our present data suggest that metformin in combination with imatinib might be a promising therapeutic option in colorectal cancer.