• Title, Summary, Keyword: antitumor

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Enhanced Production of Oleanolic Acid by the Elicitation in Oldenlandia diffusa Suspension Cell Cultures (백화사설초의 현탁세포배양에서 Elicitation에 의한 Oleanolic acid 생산성 증대)

  • Lee Yong-Il;Kim Dong-Il
    • KSBB Journal
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    • v.19 no.6
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    • pp.471-477
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    • 2004
  • Oldenlandia diffusa is a Chinese medicinal herb with antitumor activity capable of suppressing the growth of some cancer cell lines. Oleanolic acid and ursolic acid are triterpenoid compounds that exist in Oldenlandia diffusa. Recently, these have been noted for anti-inflammatory, anti-cancer, and hepato-protective effects. Application of both plant growth regulators, 2,4-D and kinetin, was found to be essential for the initiation of callus and suspension cells. Leaf blades of Oldenlandia diffusa was transformed into callus on Schenk and Hildebrandt medium supplemented with 0.5 mg/L 2,4-D and 0.1 mg/L kinetin, while optimum initiation condition for suspension cells of Oldenlandia diffusa was determined to be 0.75 mg/L 2,4-D and 0.1 mg/L kinetin. Chromatographic separation of oleanolic acid from its derivatives was achieved using Rexchrom S5-100-ODS column. Analytical conditions for oleanolic acid were determined as follows: flow rate at 1.0 mL/min, UV length at 200 nm and mobile phase of $80\%$ acetonitrile and $20\%$ water. Production of secondary metabolites was found to be increased by the treatment with elicitors or signal transducers. The maximum production of oleanolic acid was 99.6 mg/L in cultures with 0.5 mM salicylic acid. It is 1.74 times higher than that of control.

Synthetic Chenodeoxycholic Acid Derivative HS-1200-Induced Apoptosis of Human Oral Squamous Carcinoma Cells (합성 Chenodeoxycholic Acid 유도체 HS-1200이 유도한 사람구강 편평상피암종세포 세포자멸사 연구)

  • Kim, In-Ryoung;Sohn, Hyeon-Jin;Kim, Gyoo-Cheon;Kwak, Hyun-Ho;Park, Bong-Soo;Choi, Won-Chul;Ko, Myung-Yun;Ahn, Yong-Woo
    • Journal of Oral Medicine and Pain
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    • v.32 no.3
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    • pp.251-261
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    • 2007
  • Bile acids and synthetic its derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. Previous studies have been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis inducing activity on various cancer cells in vitro. It wasn't discovered those materials have apoptosis induced effects on YD9 human oral squamous carcinoma cells. The present study was done to examine the synthetic bile acid derivatives(HS-1199, HS-1200) induced apoptosis on YD9 cells and such these apoptosis events. We administered them in culture to YD9 cells. Tested YD9 cells showed several lines of apoptotic manifestation such as activation of caspase-3, degradation of DFF, production of poly (ADP-ribose) polymerase(PARP) cleavage(HS-1200 only), DNA degradation(HS-1200 only), nuclear condensation, inhibition of proteasome activity, reduction of mitochondrial membrane potential(HS-1200 only) and the release of cytochrome c and AIF to cytosol. Between two synthetic CDCA derivatives, HS-1200 showed stronger apoptosis-inducing effect than HS-1199. Therefore HS-1200 was demonstrated to have the most efficient antitumor effect. Taken collectively, we demonstrated that a synthetic CDCA derivative HS-1200 induced caspases-dependent apoptosis via mitochondrial pathway in human oral sqauamous carcinoma cells in vitro. Our data therefore provide the possibility that HS-1200 could be considered as a novel therapeutic strategy for human orall squamous carcinoma from its poweful apoptosis-inducing activity.

Immune Cell Activation and Co-X-irradiation Effect of Eleutherococcus senticosus Maxim Root (가시오갈피 뿌리의 면역세포 활성 및 방사선 병용효과)

  • Kwon, Hyoung-Cheol;Park, Jeong-Seob;Choi, Dong-Seong
    • Radiation Oncology Journal
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    • v.25 no.3
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    • pp.185-191
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    • 2007
  • Purpose: This study was performed to investigate the effects of immune cell activation and the antitumor effect for the combination of treatment with X-irradiation and E/eutherococcus senticosus Maxim Root (ESMR) on mouse tumor cells. Materials and Methods: ESMR (250g) was extracted with 80% methanol, concentrated under decompression and lyophilized. To determine whether ESMR is able to activate the immune cells or not, the proliferation of splenocytes in vitro and the number of B cells and T cells in splenic lymphocytes in ESMR-pretreated mice were evaluated. X-irradiation was given to the mouse fibrosarcoma tumor cells (FSa II) by 250 kv X-irradiation machine. The cytotoxicity of ESMR was evaluated from its ability to reduce the clonogenecity of FSa II cells. In X-irradiation alone group, each 2, 4, 6 and 8 Gy was given to FSa II cells. In X-irradiation with ESMR group, 0.2 mg/ml of ESMR was exposed to FSa II cells for 1 hour before X-irradiation. Results: The proliferation of cultured mouse splenocytes and thymocytes were enhanced by the addition of ESMR in vitro. The number of B cells and T cells in mouse splenic lymphocytes was significantly increased in ESMR pretreated mice in vivo. In FSa II cells that received a combination of 0.2 mg/ml of ESMR with X-irradiation exposure, the survival fraction with a dose of 2, 4 and 6 Gy was $0.39{\pm}0.005$, $0.22{\pm}0.005$ and $0.06{\pm}0.007$, respectively. For FSa II cells treated with X-irradiation alone, the survival fraction with a dose of 2, 4 and 6 Gy was $0.76{\pm}0.02$, $0.47{\pm}0.008$ and $0.37{\pm}0.01$. The difference in the survival fraction of the mouse FSa II cells treated with and without ESMR was statistically significant (p<0.05). Conclusion: Treatment with ESMR increased cell viability of mouse splenocytes in vitro and especially the subpopulation of B cells and T cells in splenocytes in ESMR-pretreated mice. However, treatment with ESMR did not increase the level of Th and Tc subpopulations in the thymocytes. Treatment with the combination of ESMR and X-irradiation was more cytotoxic to mouse tumor cells than treatment with X-irradiation alone; this finding was statistically significant.

Trends of mushroom science and mushroom industry (버섯과학과 버섯산업의 동향)

  • Yoo, Young-Bok;Kong, Won-Sik;Oh, Se-Jong;Cheong, Jong-Chun;Jang, Kab-Yeul;Jhune, Chang-Sung
    • Journal of Mushroom
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    • v.3 no.1
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    • pp.1-23
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    • 2005
  • World production of mushrooms has been increasing 10-20% every year. Recently, Pleurotus eryngii and P. nebrodensis are very popular as new mushroom species for cultivation. Two kinds of mushrooms, Gumji (Ganoderma) and Soji, were described in old book of Samguksagi (History of the three kingdoms; 1145) in Koryo-dynasty. Many kinds of mushrooms were also described in more than 16 kinds of old books during Chosun-dynasty in Korea. One hundred and sixty commercial strains of 25 species in mushrooms were distributed to cultivators. By the way, only 8 varieties of them have registered variety protection. Mushroom industry as important export products developed from 1960 to 1980. Production of mushrooms as food was 181,828 metric tons valued at 800 billion Korean won in 2003. Isolated and identified substances from mushrooms are promising antifungal, antiinflammatory, antitumor, antiviral (anti-HIV), antibacterial & antiparasitic, antidiabetic, immunomodulating, kidney tonic, hepatoprotective, nerve tonic, and sexual potentiator. These substances can also be used for blood pressure regulation and effective against cardiovascular disorders, hypocholesterolemia & hyperlipidemia, and chronicbronchitis. Mushroom products including pharmaceuticals, tonics, healthy beverages, functional biotransformants, and processed foods have also became available on the markets. Compost and feed can likewise be made from mushroom substrates after harvest. The mushroom industry is already one of the fastest growing investment sectors in Korea. By the way, there is a need to strain improvement for variety protection, advanced cultivation technology at low cost for growers, and control of demand and supply for marketing in order to more upgrade development of mushroom industry in the future.

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Immunohistochemical Study of Phosphatase and Tensin Homolog Deleted on Chromosome Ten in Gefitinib Treated Nonsmall Cell Lung Cancer Patients (폐암 조직에서의 PTEN 발현 정도와 Gefitinib의 반응율과의 관계)

  • Lee, Sung Yong;Lee, Ju Han;Jung, Jin Yong;Lee, Kyoung Ju;Lee, Seung Hyeun;Kim, Se Joong;Lee, Eun Joo;Hur, Gyu Young;Jung, Ki Hwan;Jung, Hye Cheol;Lee, Sang Yeub;Kim, Je Hyeong;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.5
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    • pp.473-479
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    • 2005
  • Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

The Synthesis of the Stable IVDU Derivative for Imaging HSV-1 TK Expression (체내 안정형 HSV1-tk (Herpes Simplex Virus Type-1 Thymidine Kinase) 영상용 IVDU 유도체의 합성)

  • Kim, Eun-Jung;Choi, Tae-Hyun;Ahn, Soon-Hyuk;Kim, Byoung-Soo;Park, Hyun;Cheon, Gi-Jeong;Rhee, Hak-June;An, Gwang-Il
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.5
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    • pp.478-486
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    • 2009
  • Purpose: 5-iododeoxyuridine analogues have been exclusively developed for the potential antiviral and antitumor therapeutic agents. In this study, we synthesized carbocyclic radioiododeoxyuridineanalogue (ddIVDU) and carbocyclic intermediate as efficient carbocyclic radiopharmaceuticals. Materials and Methods: The synthesis is LAH reduction, hetero Diels-Alder reaction as key reactions including Pd(0)-catalyzed coupling reaction together with organotin. MCA-RH7777 (MCA) and MCA-tk (HSV1-tk positive) cells were treated with various concentration of carbocyclic ddIVDU, and GCV. Cytotoxicity was measured by the MTS methods. For in vitro uptake study, MCA and MCA-tk cells were incubated with 1uCi of [$^{125}I$]carbocyclic ddIVDU. Accumulated radioactivity was measured after various incubation times. Results: The synthesis of ddIVDU and precursor for radioiodination were achieved from cyclopentadiene in good overall yield, respectively. The radioiododemetallation for radiolabeling gave more than 80% yield with > 95% radiochemical purity. GCV was more toxic than carbocyclic ddIVDU in MCA-tk cells. Accumulation of [$^{125}I$]carbocyclic ddIVDU was higher in MCA-tk cells than MCA cells. Conclusion: Biological data reveal that ddIVDU is stable in vitro, less toxic than ganciclovir (GCV), and selective in HSV1-tk expressed cells. Thus, this new carbocyclic nucleoside, referred to in this paper as carbocyclic 2',3'-didehydro-2',3'-dideoxy-5- iodovinyluridine (carbocyclic ddIVDU), is a potential imaging probe for HSV1-tk.

Induction of Apoptosis and G2/M Cell Cycle Arrest by Cordycepin in Human Prostate Carcinoma LNCap Cells (Cordycepin에 의한 LNCap 인체 전립선 암세포의 apoptosis 및 G2/M arrest 유발)

  • Lee, Hye Hyeon;Hwang, Won Deok;Jeong, Jin-Woo;Park, Cheol;Han, Min Ho;Hong, Su Hyun;Jeong, Yong Kee;Choi, Yung Hyun
    • Journal of Life Science
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    • v.24 no.1
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    • pp.92-97
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    • 2014
  • Cordycepin, an active component originally isolated from the traditional medicine Cordyceps militaris, is a derivative of the nucleoside adenosine, which has been shown to possess a number of pharmacological properties, including antioxidant and anti-inflammatory activities, immunological stimulation, and antitumor effects. This study was conducted on cultured human prostate carcinoma LNCap cells to elucidate the possible mechanisms by which cordycepin exerts its anticancer activity, which, until now, has remained poorly understood. Cordycepin treatment of LNCap cells resulted in dose-dependent inhibition of cell growth and the induction of apoptotic cell death as detected by an MTT assay, cleavage of poly ADP-ribose polymerase, and annexin V-FITC staining. Flow cytometric analysis revealed that cordycepin resulted in G2/M arrest in cell cycle progression and downregulation of cyclin B1 and cyclin A expression in a concentration-dependent manner. Moreover, the incubation of cells with cordycepin caused a striking induction in the expression of the cyclin-dependent kinase (CDK) inhibitor p21Waf1/Cip1 without affecting the expression of the tumor suppressor p53. It also resulted in a significant increase in the binding of CDK2 and CDC2 to p21. These findings suggest that cordycepin-induced G2/M arrest and apoptosis in human prostate carcinoma cells is mediated through p53-independent upregulation of the CDK inhibitor p21.

The Anti-angiogenic Potential of a Phellodendron amurense Hot Water Extract in Vitro and ex Vivo (in Vitro와 ex vivo에서 황백 온수추출물의 신생혈관 억제효과)

  • Kim, Eok-Cheon;Kim, Seo Ho;Bae, Kiho;Kim, Han Sung;Gelinsky, Michael;Kim, Tack-Joong
    • Journal of Life Science
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    • v.25 no.6
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    • pp.693-702
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    • 2015
  • Blocking new blood-vessel formation (angiogenesis) is now recognized as a useful approach to the therapeutic treatment of many solid tumors. The best validated approach to date is to target the vascular endothelial growth-factor (VEGF) pathway, a key regulator of angiogenesis. Many natural products and extracts that contain a variety of chemopreventive compounds have been shown to suppress the development of malignancies through their anti-angiogenic properties. Phellodendron amurense, which is widely used in Korean traditional medicine, has been shown to possess antitumor, antimicrobial, and anti-inflammatory properties, among others. The present study investigated the effects of P. amurense hot-water extract (PAHWE) on angiogenesis, a key process in tumor growth, invasion, and metastasis. To investigate PAHWE’s anti-angiogenic properties, this study’s authors performed an analysis of angiogenesis and endothelial-cell proliferation, migration, invasion, and tube formation, as well as zymogram assays and the rat aortic ring-sprouting assay. PAHWE inhibited cell growth, mobility, and vessel formation in response to VEGF in vitro and ex vivo. Furthermore, it reduced VEGF-induced intracellular signaling events, such as the activation of matrix metalloproteinases (MMPs) -2 and -9. These results indicate that PAHWE’s anti-angiogenic properties might lead to the development of potential drugs for treating angiogenesis-associated diseases such as cancer.

The Effect of Two Terpenoids, Ursolic Acid and Oleanolic Acid on Epidermal Permeability Barrier and Simultaneously on Dermal Functions (우솔릭산과 올레아놀산이 피부장벽과 진피에 미치는 영향에 대한 연구)

  • Suk Won, Lim;Sung Won, Jung;Sung Ku, Ahn;Bora, Kim;In Young, Kim;Hee Chang , Ryoo;Seung Hun, Lee
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.2
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    • pp.263-278
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    • 2004
  • Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromerol and malol, are pentacyclic triterpenoid compounds which naturally occur in a large number of vegetarian foods, medicinal herbs, and plants. They may occur in their free acid form or as aglycones for triterpenoid saponins, which are comprised of a triterpenoid aglycone, linked to one or more sugar moieties. Therefore UA and ONA are similar in pharmacological activity. Lately scientific research, which led to the identification of UA and ONA, revealed that several pharmacological effects, such as antitumor, hepato-protective, anti-inflammatory, anticarcinogenic, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effect of UA and ONA on acutely barrier disrupted and normal hairless mouse skin. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery, both flanks of 8-12 week-old hairless mice were topically treated with either 0.01-0.1mg/mL UA or 0.1-1mg/mL ONA after tape stripping, and TEWL (transepidermal water loss) was measured. The recovery rate increased in those UA or ONA treated groups (0.1mg/mL UA and 0.5mg/mL ONA) at 6h more than 20% compared to vehicle treated group (p < 0.05). Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. For verifying the effects of UA and ONA on normal epidermal barrier, hydration and TEWL were measured for 1 and 3 weeks after UA and ONA applications (2mg/mL per day). We also investigated the features of epidermis and dermis using electron microscopy (EM) and light microscopy (LM). Both samples increased hydration compared to vehicle group from 1 week without TEWL alteration (p < 0.005). EM examination using RuO4 and OsO4 fixation revealed that secretion and numbers of lamellar bodies and complete formation of lipid bilayers were most prominent (ONA=UA > vehicle). LM finding showed that thickness of stratum corneum (SC) was slightly increased and especially epidermal thickening and flattening was observed (UA > ONA > vehicle). We also observed that UA and ONA stimulate epidermal keratinocyte differentiation via PPAR Protein expression of involucrin, loricrin, and filaggrin increased at least 2 and 3 fold in HaCaT cells treated with either ONA (10${\mu}$M) or UA (10${\mu}$M) for 24 h respectively. This result suggested that the UA and ONA can improve epidermal permeability barrier function and induce the epidermal keratinocyte differentiation via PPAR Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber elongation by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory activity measurements were also confirmed in vivo findings. These data suggested that the effects of UA and ONA related to not only epidermal permeability barrier functions but also dermal collagen and elastic fiber synthesis. Taken together, UA and ONA can be relevant candidates to improve epidermal and dermal functions and pertinent agents for cosmeseutical applications.

Effect of Solvent Fractions from Doenjang on Antimutagenicity, Growth of Tumor Cells and Production of Interleukin-2 (된장 분획물의 항돌연변이 및 암세포 증식 억제효과와 interleukin-2 생성에 미치는 영향)

  • Kim, Kwang-Hyuk;Park, Kun-Young;Lee, Sook-Hee;Lim, Sun-Young
    • Journal of Life Science
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    • v.17 no.6
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    • pp.791-797
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    • 2007
  • We studied the inhibitory effect of solvent fractions from doenjang on mutagenicity using Salmonella typhimurium TA100 in Ames test. We also investigated the effect of solvent fractions from doenjang on the growth of tumor cells and the production of interleukin-2 (IL-2). The treatment of dichlorormethane and ethylacetate fractions (2.5 mg/assay) from doenjang to Ames test system inhibited aflatoxin B$_1$ (AFB$_1$) induced mutagenicity by 96% and 97%, respectively, and showed a higher antimutagenic effect than other solvent fractions. In case of N-methyl-N'-nitro-N-nitrosoguamidine (MNNG) induced mutagenicity, the ethylacetate fraction showed the highest inhibitory effect (by 75%) among the other sol-vent fractions, although the inhibitory effect was not stronger compared to AFB$_1$ induced mutagenicity. The treatment of dichloromethane and ethylacetate fractions markedly inhibited the growth of Yac-1 (by 80% and 94%, respectively) and sacroma-180 cancer cells (by 60% and 96%, respectively) after 4 days of incubation at 37${\circ}$C. To elucidate the immunological mechanism of antitumor activity of doenjang, spleen cells of Balb/c mouse were exposed to the dichloromethane and ethyl-acetate fractions for 24 hours at 37${\circ}$C . The culture supernatants following the treatment of djchloromethane and ethylacetate factions to spleen cells increased the production of IL-2. These results indicated that the anticarcinogenic effect of doenjang was mediated by the production of IL-2.