• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.89-94
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• 1998

Marine sponges are recognized as a plentiful source of diverse biologically active secondary metabolites. Recently, we have initiated a research to discover antitumor constituents from the marine sponges collected from Korean Waters. Marine sponges collected from the South Sea of Korea were screened for several biological activities including such as brine shrimp lethality and cytotoxicity. Significant brine shrimp lethality was detected in the crude extract of a two-sponge association of Poecillastra sp. and Jaspis sp. A cross-section of this sample showed two layers of morphologically distinct sponges. The thin and dirty yellow outer layer was identified as Poecillastra sp. (Pachastrellidae), the surface of which was very rough. The light-grey inner layer was identified as Jaspis sp. (Jaspidae), the surface of which was smooth. This two-sponge association appears to be consistent as these sponges were always found in associated form regardless of collection site or collection period. Investigation of the bioactive constituents monitored by brine shrimp lethality assay led to the isolation of pectenotoxin II (PTX2) and psammaplin A as causative compounds for the brine shrimp lethality. $^1$H- and $\^$13/C-nmr signals of PTX2 was fully assigned utilizing TOCSY, HETCOR, Long-range HETCOR, and Homonuclear J-resolved 2D experiments. PTX2 displayed very potent and selective cytotoxicities in the 60 cell line panel antitumor assay at the NCI. PTX2 has progressed to acute toxicity determination and in vivo antitumor assay at the NCI (Table 1). However, significant in vitro antitumor activity of PTX2 can not be affirmed in the in vivo assay.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.185-196
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• 1992

To assess its suitability as a prodrug of 5-fluorouracil (5-FU), 1-glycyloxymethyl-5-FU HCl (GFU), a 5-fluorouracil derivative having a glycyloxymethyl group at the N-l position was synthetized. Its physicochemical properties and hydrolysis kinetics, in aqueous solution of pH $1{\sim}10$ and in the presence of human plasma or rat liver homogenate were studied. Its acute toxicity and antitumor activity against sarcoma 180 were also examined, GFU showed higher lipid/water partition coefficient than 5-FU. The calculated $pK_{\alpha}$ values of 5-FU and GFU were 8.02 and 7,20, respectively. The decomposition rates of GFU in aqueous solution showed a pH-dependence over the pH range used, which could be ascribed to solvent catalysed hydrolysis reaction at pH lower than 4,16 and to specific hydroxide ion hydrolysis reaction at pH higher than 4,16, The half-life of GFU was 6,9 min in 80% human plasma solution and less than 3 min in rat liver homogenate at $37^{\circ}C$, The $LD_{50}$ value of 5-FU was 240 mg/kg while that of GFU was 440.6 mg/kg (226 mg as 5-FU). Both of 5FU and GFU showed a strong antitumor activity, Therapeutic ratios of 5-FU and GFU were 3.07 and 3.55, respectively.

• Korean Journal of Medicinal Crop Science
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• v.18 no.3
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.98-98
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• 2003

${\beta}$-(1,3)-D-Glucans have been known to exhibit antitumor and antimicrobial activities. The presence of dectin-1,${\alpha}$, ${\beta}$-glucan receptor of dendritic cell, on macrophage has been controvertial. RT-PCR analysis led to the detection of dectin-1${\alpha}$ and ${\beta}$ in murine macrophage Raw264.7 cell line. Among the various organs of mouse, dectin-1${\alpha}$ and ${\beta}$ were detected in the thymus, lung, spleen, stomach and intestine. To analyze gene expression modulated by ${\beta}$-glucan treated murine Raw264.7 macrophage, total mRNA was applied to cDNA microarray to interrogate the expression of 7,000 known genes. cDNA chip analysis showed that ${\beta}$-glucan of P. osteatus increased gene expressions of immunomodulating genes, membrane antigenic proteins, chemokine ligands, complements, cytokines, various kinases, lectin associated genes and oncogenes in Raw 264.7 cell line. When treated with ${\beta}$-glucan of P. osteatus and LPS, induction of gene expression of TNF-${\alpha}$ and IFN-R1 was confirmed by RT-PCR analysis. Induction of TNF-R type II expression was confirmed by FACS analysis. IL-6 expression was abolished by EDTA in ${\beta}$-glucan and LPS treated Raw264.7 cell line, indicating that ${\beta}$-glucan binds to dectin-l in a Ca$\^$＋＋/ -dependent manner. To increase antitumor efficacy of ${\beta}$-glucan, ginsenoside Rh2 (GRh2) was co-treated with ${\beta}$-glucan in vivo and in vitro tests. IC$\sub$50/ values of GRh2 were 20 and 25 $\mu\textrm{g}$/$m\ell$ in SNU-1 and B16 melanoma F10 cell line, respectively. Co-treatment with ${\beta}$-glucan and GRh2 showed synergistic antitumor activity with cisplatin and mitomycin C both in vitro and in vivo. Single or co-treatment with ${\beta}$-glucan and GRh2 increased tumor bearing mouse life span. Co-treatment with ${\beta}$-glucan and GRh2 showed more increased life span with mitomycin C than that with cisplatin. Antitumor activities were 67% and 72 % by co-injection with ${\beta}$-glucan and GRh2 in the absence or presence of mitomycin C, respectively.

• Korean Journal of Pharmacognosy
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• v.45 no.1
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• pp.1-10
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• 2014

Ginsenoside Rg3 (G-Rg3) is one of protopanaxadiol ginsenosides characteristic of red ginseng, steamed and dried ginseng (Panax ginseng), which has recently attracted much attention for its antitumor properties in vitro and in vivo animal models. Experimental studies have demonstrated that it could promote cancer cell apoptosis, inhibit cancer cell growth, the apoptosis of cancer cells, adhesion, invasion and metastasis, and also prevent an angiogenetic formation in prostate, breast, ovarian, colorectal, gastric, liver and lung cancer etc. It has shown the antitumor activities by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins), growth factors (vascular endothelial growth factor), tumor suppressors (p53 and p21), cell death mediators (caspases, Bcl-2, Bax), inflammatory response molecules ($NF-{\kappa}B$ and COX-2), protein kinases (JNK, Akt, and AMP-activated protein kinase) and Wnt/${\beta}$-catenin signaling. In addition, the combination of Rg3 and chemotherapeutic agents have synergistically enhanced therapeutic efficacy and reduced antagonistically side effects. Furthermore, it can reverse the multidrug resistance of cancer cells, prolong the survival duration and improve life quality of cancer patients. Taken together, accumulating evidences could provide the potential of G-Rg3 in the treatment of cancers and the feasibility of further randomized placebo controlled clinical trials.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.109-109
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• 1997

Inhibitory effect on DNA topoisomerase-I, rate of glutathione conjugation and cytotoxicity of naphthoquinone derivatives were correlated. During 5 min exposure of the derivatives to glutathione (GSH), it was found that 14% of 5,8-dimethoxy-1,4-naphthoquinone(DMNQ) was converted into a GSH-conjugate, whereas 5,8-dihydroxy-1,4-naphthoquinone(DHNQ) did not interact with GSH, implying that DMNQ exerted higher electrophilicity than DHNQ. However, DHNQ (IC$\_$50/, 0.15 ${\mu}$M) showed stronger cytotoxicity in L1210 cells than DMNQ(IC$\_$50/, 0.45 ${\mu}$M). The stronger cytotoxicity of DHNQ, compared to DMNQ, could be ascribed to more rapid redox cycling. Both naphthoquinones (IC$\_$50/, 60-65 ${\mu}$M) exhibiting about the same inhibitory effect on DNA topoisomerase-I were more potent than 1,4-naphthoquinone(1,4-NQ, IC$\_$50/, 134 ${\mu}$M). Thus, 5,8-oxy groups in the structure seem to be important for the inhibition of the enzyme. DMNQ showed a broader dose range while maintaining a good antitumor activity against S-180 fluid tumor. For these reasons, DMNQ was taken as useful pharmacophore for structural modification. Introduction of 1-hydroxyalkyl groups at C-2 of DMNQ lowered all of the activities mentioned above, while acetylation of 1-hydroxyalkyl moiety enhanced the activities by 4-5 times. Introduction of the same side chains at C-6 exhibited stronger activities than 2-substituted ones. Based on these results it was suggested that the quinonoid moiety in 6-substituted DMNQ was more exposed to cellular nucleophiles such as DNA, thiols of enzymes and so on. The synthesis of DHNQ or DMNQ derivatives are going on, and the corelationship between structure-activity will be discussed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7641-7651
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• 2015

It has been shown previously that nutritional supplements rich in polyphenolic compounds play a significant role in prostate cancer chemoprevention. Propolis is a natural, resinous hive product that has several pharmacological activities including antimicrobial, antioxidant, anti-inflammatory, and antitumoral activities. The aim of this study was to compare the cytotoxic, antioxidant and antitumoral activities of an ethanolic extract of Egyptian propolis (EEP) in vitro with an established chemotherapeutic drug such as doxorubicin (DOX), and the effects of their combination against the PC3 human prostate cancer cell line. Cellular viability and $IC_{50}$ levels with EEP, DOX and their (v/v) combination were detected by sulphorhodamine-B (SRB) assay after incubation of PC3 cells for 72h with different doses (0, 0.01, 0.1, 1, 10 and $100{\mu}g/ml$). Two selected doses of $IC_{50}$ and $IC_{25}$ were applied to cells for 24h for antitumor evaluation assay of treatment compounds. EEP and its (v/v) combination with DOX showed significant antitumor potential besides high antioxidant properties of superoxide dismutase (SOD), total antioxidant capacity (TAC), catalase (CAT), nitric oxide (NO) and reduced glutathione (GSH) levels when compared with the control untreated cells. DNA fragmentation assay and semi quantitative RT-PCR analyses for p53 and Bax genes showed that EEP activated cellular apoptosis and increased the mRNA expression levels more than other treatment. In conclusion, EEP alone or in combination with DOX at both doses used here showed greater antioxidant, antiproliferative and apoptotic effects against the PC3 cell lines as compared to treatment with DOX alone. Therefore, EEP could be considered as a promising candidate for prostate cancer chemotherapy.

• Journal of Society of Preventive Korean Medicine
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• v.5 no.1
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• pp.144-150
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• 2001

The cytotoxic activity of Cratalariae sessiliflorae on cultured NIH 3T3 fibroblasts and human oral epithelioid carcinoma cells (KB) were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) colorimetric method These fractions of methanol extract of Cratalariae sessiliflorae showed inhibitory effect in vitro in the milligram range against KB cell lines. In general, the antitumor activities of these fractions were does-dependent over the milligram range. The comparison of IC50 values of these fractions in tumor cell lines showed that their susceptibility to these fractions decrease in the following order: Fr. 4> Fr. 6> Fr. 10> Fr. 2> Fr. 11> Fr. 3> Fr. 8> Fr. 7> Fr. 9> Fr. 1> Fr. 5 by the MTT assay. These fractions were tested for their cytotoxic effects on NIH 3T3 fibroblasts using MTT assay. They exhibited potent cytotoxic activities in vitro in the milligram range against NIH 3T3 fibroblasts. In general, the cytotoxic activities of these fractions were does-dependent over the milligram range. The comparison of CD50 values of these fractions in NIH 313 fibroblasts shows that their susceptibility to these fractions in decrease the following order: Fr. 10> Fr. 9> Fr. 2 = Fr. 4> Fr. 8> Fr. 11> Fr. 1 = Fr. 7> Fr. 3> Fr. 5 = Fr. 6 by the MTT assay. These results suggests that fraction 5 has the most growth - inhibitory activity against KB cell lines.

• Korean Journal of Pharmacognosy
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• v.28 no.1
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• pp.54-58
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• 1997

The cytotoxic activities of methanolic extract and its fractions of Ailanthi Cortex Radicis and column chromatographic eluates of its dichloromethane fraction (DCM fr.) were investigated. DCM fr. Showed the strongest cytotoxicity against hepatoma cells. Furthermore, the active equates 1-3, 8 and 9 were obtained. Effects on free radical generation and the growth of vascular endothelial cells were tested to elucidate the action mechanism of anticancer activity. Eluates 1-3 stimulated free radical generation, while eluates 8 and 9 showed no changes. Especially, eluates 8 and 9 efffectively inhibited the proliferation of vascular endothelial cells in a dose- dependant manner. It is speculated that the anticancer effects of eluates 1-3, 8 and 9 might be due to free radical generation and inhibition of endothelial cell growth, respectively.

• Mycobiology
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• v.40 no.3
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• pp.181-188
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• 2012

This study was initiated in order to investigate the anticancer and immunomodulating activities of crude polysaccharides extracted in methanol, neutral saline, and hot water (hereinafter referred to as Fr. MeOH, Fr. NaCl, and Fr. HW, respectively) from the fruiting bodies of Panellus serotinus. Content of ${\beta}$-glucan and protein in Fr. MeOH, Fr. NaCl, and Fr. HW extracts of P. serotinus ranged from 22.92~28.52 g/100 g and 3.24~3.68 g/100 g, respectively. In vitro cytotoxicity tests, none of the various fractions of crude polysaccharides were cytotoxic against sarcoma 180, HT-29, NIH3T3, and RAW 264.7 cell lines at the tested concentration. Intraperitoneal injection with crude polysaccharides resulted in a life prolongation effect of 23.53~44.71% in mice previously inoculated with sarcoma 180. Treatment with Fr. HW resulted in an increase in the numbers of spleen cells by 1.3 fold at the concentration of $50{\mu}g/mL$ compared with control. Treatment with Fr. NaCl resulted in improvement of the immuno-potentiating activity of B lymphocytes by increasing the alkaline phosphatase activity by 1.4 fold, compared with control, at the concentration of $200{\mu}g/mL$. Among the three fractions, maximum nitric oxide ($13.48{\mu}M$) was recorded at $500{\mu}g/mL$ in Fr. HW. Production of tumor necrosis factor alpha, interleukin-$1{\beta}$, and interleukin-6 was significantly higher, compared to the positive control, concanavalin A, at the tested concentration. Therefore, treatment with crude polysaccharides extracted from the fruiting body of P. serotinus could result in improvement of antitumor activity.