韓醫學의 抗腫瘍 免疫治療에 관한 연구 : 1990年 以後 發표된 實驗論文을 中心으로

강연이,김태임,박종오,김성훈,박종대,김동희 대한동의생리학회,대한동의병리학회 2003 동의생리병리학회지 Vol.17 No.1

This study was done to compile 104 experimental theses which are related to the antitumor and immuno-activating therapies between February 1990 through February 2002. Master's and doctoral theses were classified by schools, degrees, materials, effects, experimental methods of antitumor and immunoactivity, and results. The following results were obtained from this study : 1. Classifying the theses by the school, 34.6% were presented by Daejeon University, 29.8% by Kyung-hee University and 11.5% by Won-kwang University. Of all theses, 51.0% were aimed for the doctoral degree and 43.3% were for the master's degree. All of three universities have their own cancer center. 2. Classifying the theses by herb materials, complex prescription accounted for 60.3%, single herb accounted for 24.8% and herbal acupuncture accounted for 14.2%. Considering the key principles of the traditional medicine, complex prescription was much more thoroughly studied than single herb prescription. The results showed that the complex prescription had both antitumor activity and immuno-activating activity, which might reflects on multi-actibvation mechanisms by complex components. 3. Classifying the theses by the efficacy of herbs examined, in single herb, invigorating spleen and supplementing was 35.5%, expelling toxin and cooling was 29.0%, activating blood flow and removing blood stasis was 12.9%. In herbal acupuncture, invigorating spleen and supplementing was 52.9%, expelling toxin and cooling was 29.4%. In complex prescription, pathogen-free status was 41.9%, strengthening healthy qi to eliminate pathogen was 35.5%, strengthening healthy qi was 22.6%. It is presumed that the antitumor and immunoactivating therapy based on syndrome differentiation is the best way to develop oriental oncology. 4. Classifying the theses by an antitumor experiments, cytotoxic effect was 48.1%, survival time was 48.1%, and change of tumor size was 42.3%. Survival rate was not necessarily correlated with cytotoxicity. These data reflect the characteristic, wholistic nature of the oriental medicine which is based on BRM (biological response modifier). 5. Classifying the theses by immunoactivating experiments, hemolysin titer was 51.0%, hemagglutinin titer was 46.2% and NK cell's activity was 44.2%. In the future studies, an effort to elucidate specific molecular and cellular mechanisms of cytokine production in the body would be crucial. 6. Classifying the theses according to the data in terms of antitumor activity, 50% was evaluated good, 24.0% was excellent, and 15.5% have no effect. In an evaluation of immuno-activating activity, 35.9% was excellent and 18.0% showed a little effect. The index point, as described here, may helps to use experimental data for clinical trials. Changes in index points by varying dosage implicate the importance of oriental medical theory for prescription. 7. In 167 materials, IIP (immunoactivating index point mean : 3.12±0.07) was significantly higher than AIP(antitumor index point, mean : 2.83±0.07). These data demonstrate to the effect of herb medicine on tumor activity depends more on immunoactivating activity than antitumor activity. This further implies that the development of herbal antitumor drugs must be preceded by the mechanistic understanding of immnunoactivating effect. 8. After medline-searching tumor and herb-related articles from NCBI web site, we conclude that most of the studies are primarily focused on biomolecular mechanisms and/or pathways. Henceforth, we need to define the biomolecular mechanisms and/or pathways affected by herbs or complicated prescriptions. 9. Therefore, the most important point of oriental medical oncology is to connect between experimental results and clinical trials. For the public application of herbal therapy to cancer, it is critical to present the data to mass media. 10. To develop the relationship of experimental results and clinical trials, university's cancer clinic must have a long-range plan related to the university laboratories and, at the same time, a regular consortium for this relationship is imperative. 11. After all these efforts, a new type herbal medicine for cancer therapy which is to take care of the long-term administering and safety problem must be developed. Then, it would be expected that anti-tumor herbal acupuncture can improve clinical symptoms and quality of life (OOL) for cancer patients. 12. Finally, oriental medical cancer center must be constructed in NCC (National Cancer Center) or government agency for the development of oriental medical oncology which has international competitive power.

Antitumor Activity of Cell Suspension Culture of Green Tea Seed (Camellia sinensis L.)

Choi, Jae-Hoon,Yoon, Sang-Kun,Lee, Keyong-Ho,Seo, Min-Soo,Kim, Doo-Hwan,Hong, Seung-Beom,Kim, Ji-Yeon,Paik, Hyun-Dong,Kim, Chang-Han The Korean Society for Biotechnology and Bioengine 2006 Biotechnology and Bioprocess Engineering Vol.11 No.5

The objective of this study was to investigate the antitumor activity of suspension cultures of tea callus cells grown in the presence of different concentrations of the growth regulator 2,4-dichlorophenoxy acetic acid (2,4-D) with or without light irradiation. The methanol and ethanol extracts of precipitated cells (MEP, EEP) exhibited stronger inhibitory effects on the growth of tumor cell lines than the water extract of precipitated cells (WEP) or the supernatant Compared to culture under dark conditions, exposure to light irradiation led to significantly higher antitumor activity. The MEP from light irradiated cells at $250{\mu}g/mL$ with 2.0mg/L 2,4-D displayed more than 64% growth inhibition of HEP-2 cells, whereas normal cells showed less than 25% growth inhibition. The some fractions of MEP obtained from Diaion HP-20 column chromatography displayed the majority of inhibitory activity against the HEP-2 cell line. These results show that 2,4-D, and light stimulated the synthesis of antitumor compounds.

Antitumor Activity and Antioxidant Role of Ichnocarpus frutescensAgainst Ehrlich Ascites Carcinoma in Swiss Albino Mice

Deepak K Dash,Siva S Nayak,Soma Samanta,Tirtha Ghosh,Tarun Jha,Bhim C Maiti,Tapan K Maity 한국생약학회 2007 Natural Product Sciences Vol.13 No.1

plant Ichnocarpus frutescens (Linn) R.Br. (Family-Apocynaceae) has been indicated for thethe possible antitumor activity and antioxidant role of Ichnocarpus frutescens in the mice transplanted withEhrlich ascites carcinoma (EAC). The chloroform and methanol extract of whole plant of Ichnocarpus frutescens(CEIF and MEIF) were administered intraperitoneally at the dose of 150 mg/kg and 300 mg/kg, body weight perday for 7 days after 24 h of tumor inoculation in mice. Treatment with CEIF at the dose of 150 mg/kg and300 mg/kg remarkably decreased the tumor volume, packed cell volume, viable cell count and increased thekg. Further the EAC mice treated with CEIF and MEIF showed significant decrease in the level of lipidperoxidation and significant increase in the level of antioxidant enzymes such as glutathione (GSH), superoxidedismutase (SOD) and catalase (CAT), however the decreasing and increasing capacity of CEIF was less in bothdoses as compared to MEIF. Based on these results, it can be concluded that the chloroform and methanol extactof Ichnocarpus frutescens exhibit significant antitumor and antioxidant activity in EAC bearing mice.Key wordsIchnocarpus frutescens, Ehrlich ascites carcinoma, antitumor activity, in vivo antioxidant activity.

목초액과 항암성 본초가 가미된 복합목초액의 항암 및 항전이 활성에 미치는 영향

김동희,최주선,김성훈 대한동의병리학회 2001 동의생리병리학회지 Vol.15 No.1

Antitumor and antimetastatic effects of holyessing and complex holyessing supplemented antitumor herbs were studied. Cytotoxicity against various cancer cell lines, DNA topoisomerase I, pulmonary colonization, antiangiogenesis, and T/C% to S-180 were evaluated, respectively. The results were summarized as follows; Holyessing and Ganodema japonicum and Ginseng radix was not exhibited cytotoxicity against all cell lines, while and Oldenlandiae diffusae Herba showed a potent cytotoxic activities against B16-F10 cell lines. 20 times of diluted holyessing(1:20) and 150㎍/㎖ of Ganodema japonicum and Ginseng radix were shown significantly inhibited DNA topoisomerase I activity. The T/C% was 113% in holyessing(HSL) treated group respectively in animal study with S-180. In pulmonary colonization assay by B16-F10, a number of colonies in the lungs were decreased more significantly in complex holyessing(CHSL-A, CHSL-B) supplemented with Ganodema japonicum, Ginseng radix and Oldenlandiae diffusae Herba than in control group. In vitro neovascularization assays, angiogenesis was significantly inhibited in complex holyessing treated group(CHSL-A, CHSL-B) than in control group. Holyessing(HSL) and complex holyessing(CHSL-A, CHSL-B) groups strongly inhibited angiogenesis than control by CAM assay. Holyessing(HSL) induced aoptosis and and synergistically increased by complex holyessing(CHSL-A, CHSL-B) groups supplementing antitumor herbs. Key word : antitumor activity, holyessing, Complex holyessing, Ganodema japonicum, Ginseng radix, Oldenlandiae diffusae Herba, DNA topoisomerase I activity, pulmonary colonization, neovascularization, apoptosis

Effects of the Hinge Region of Cecropin A(1-8)-Melittin 2(1-12), a Synthetic Antimicrobial Peptide on Antibacterial, Antitumor, and Vesicle-Disrupting Activity

Shin, Song-Yub,Kang, Joo-Hyun,Jang, So-Yun,Kim, KiI-Lyong,Hahm, Kyung-Soo Korean Society for Biochemistry and Molecular Biol 1999 Journal of biochemistry and molecular biology Vol.32 No.6

CA(1-8)-ME(1-12) [CA-ME], composed of cecropin A(1-8) and melittin(1-12), is a synthetic antimicrobial peptide having potent antibacterial and antitumor activities with minimal hemolytic activity. In order to investigate the effects of the flexible hinge sequence, Gly-Ile-Gly, of CA-ME on antibiotic activity, CA-ME and three analogues, CA-ME1, CA-ME2, and CA-ME3, were synthesized. The Gly-Ile-Gly sequence of Ca-ME was deleted in CA-ME1 and replaced with Pro and Gly-Pro-Gly in CA-ME2 and CA-ME3, respectively. CA-ME1 and CA-ME3 showed a significant decrease in antitumor activity and phospholipid vesicle-disrupting ability. However, CA-ME2 showed similar antitumor and vesicle-disrupting activities, as compared with CA-ME. These results suggest that the flexibility or ${\beta}$-turn induced by Gly-Ile-Gly or Pro in the central part of CA-ME may be important in the electrostatic interaction of the N-terminus cationic ${\alpha}$-helical region with the cell membrane surface and the hydrophobic interaction of the C-terminus amphipathic ${\alpha}$-helical region with the hydrophobic acyl chains in the cell membrane. CA-ME3 exhibited lower antitumor and vesicle-disrupting activities than CA-ME and CA-ME2. This result suggests that the excessive ${\beta}$-turn structure caused by the Gly-Pro-Gly sequence in CA-ME3 seems to interrupt ion channel/pore formation in the lipid bilayer. We concluded that the appropriate flexibility or bilayer. We concluded that the appropriate flexibility or ${\beta}$-turn structure provided by the central hinge is responsible for the effective antibiotic activity of the antimicrobial peptides with the helix-hinge-helix structure.

Effects of Antitumor Polysaccharides from Forsythia Corea on the lumune Function (I)

Moon, Chang-Kiu,Park, Kwang-Sik,Lee, Soo-Hwan,Ha, Bae-Jin,Lee, Byeong-Gon The Pharmaceutical Society of Korea 1985 Archives of Pharmacal Research Vol.8 No.1

Polysaccharide fractions were prepared from Forsythia Corea by several different extraction schedules. The fractions obtained were designated as ForCo A, ForCo B and ForCo C respectively. ForCo C was further purified through Sephadex G 200 column chromatography and obtianed two subfractions (Coreana A, Coreana B). ForCo showed marked antitumor activity against sarooma 180 and its activity was dose-dependent. Coreana A, purified from ForCo C, showed somewhat higher antitumor activity. ForCo C increased the number of circulating leucocytes and peritoneal exudate cells, but didn't show any significant effects on the phagocytic activity and total serum protein level. Chemical analysis showed that ForCo C was composed of glucose, galactose, xylose and arabinose. A close relationship between antitumor activities and polysaccharide contents waw observed. These results indicate strongly that antitumor active principle of Forsythia Corea is polysaccharide.

목향 추출물의 항산화 및 항암활성

송진욱,민경진,차춘근,Song, Jin-Wook,Min, Kyung-Jin,Cha, Chun-Geun 한국환경보건학회 2008 한국환경보건학회지 Vol.34 No.1

This study was carried out to investigate the antioxidative and antitumor activities of Saussurea lappa for the purpose of developing a functional food. The methanol extract of Saussurea lappa was fractionated with five solvents (hexane, chloroform, EtOAc, BuOH, water) and examined for antioxidative activities and xanthine oxidase inhibitory activity in addition to growth inhibitory activity of human cancer cell (HT-29, SNU-1, HeLa). Total phenol compound contents were higher in EtOAC fraction than other fractions. Also, electron donating ability was over 90% at $500{\mu}g/ml$ (93.1 %) and $1000{\mu}g/ml$ (94.3%). The hexane fraction revealed stronger nitrite scavenging ability than the positive control (ascorbic acid) and its abilities were 22.4% and 42.8% at $500{\mu}g/ml$ and $1000{\mu}g/ml$, respectively. Xanthine oxidase inhibitory activity had similar tendency to electron donating ability. The EtOAc fraction showed high inhibition to xanthien oxidase activities at $500{\mu}g/ml$(81.9%) and $1000{\mu}g/ml$(90.4%). In the antitumor activity test, the hexane fraction exhibited potent growth inhibition activity against HT-29, SNU-1 and HeLa cells. Therefore, we believe that Saussurea lappa can be developed into a functional food with antioxidant activity. Additional studies are required for the hexane and chloroform fractions of Saussurea lappa to develop them into therapeutic supplements for stomach cancer, colon cancer, and cervical cancer.

Synthesis and Evaluation of Antitumor Activity of Novel 1,4-Naphthoquinone Derivatives (IV)

Kim Bok Hee,Yoo Jikang,Park Si-Hyun,Jung Jae-Kyung,Cho Hoon,Chung Yongseog The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.2

1,4-Naphthoquinones are widely distributed in nature and many clinically important antitumor drugs containing a quinone moiety, such as anthracyclines, mitoxantrones and saintopin, show excellent anticancer activity. In this study, 2- or 6-substituted 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) and 5,8-dihydroxy-1,4-naphthoquinone (DHNQ) derivatives were synthesized, and their cytotoxic activity against L1210 and P388 cancer cells was examined. Their antitumor activity was also assessed in mice bearing S-180 cells in the peritoneal cavity. In comparison with the DMNQ derivatives, the DHNQ derivatives exhibited more potent bioactivities than the DMNQ derivatives against both L1210 and P388 cells in vitro and S-180 cells in vivo. The $ED_{50}$ values of the DHNQ derivatives against P388 cells were in the range of 0.18-1.81 ${\mu}g/mL$ whereas those of the DMNQ derivatives were in the range of 0.26-40.41 ${\mu}g/mL$. The T/C ($\%$) values of the DHNQ derivatives, 8, 17, 18, 19, and 20, were found to be comparable to or even better than that of adriamycin. It was also observed that the 2-substituted derivatives (8, 19, 20) showed better antitumor activity than the 6-substituted derivatives (7, 17, 18) in the mice bearing S-180 cells in the peritoneal cavity.

Effects of artemisinin and its derivatives on growth inhibition and apoptosis of oral cancer cells

Nam, Woong,Tak, Jungae,Ryu, Ju-Kyoung,Jung, Mankil,Yook, Jong-In,Kim, Hyung-Jun,Cha, In-Ho Wiley Subscription Services, Inc., A Wiley Company 2007 Head & neck Vol.29 No.4

<B>Background.</B><P>Artemisinin is of special biological interest because of its outstanding antimalarial activity. Recently, it was reported that artemisinin has antitumor activity. Its derivatives, artesunate, arteether, and artemeter, also have antitumor activity against melanoma, breast, ovarian, prostate, CNS, and renal cancer cell lines. Recently, monomer, dimer, and trimer derivatives were synthesized from deoxoartemisinin, and the dimers and the trimers were found to have much more potent antitumor activity than the monomers.</P><B>Methods.</B><P>We evaluated the antitumor activity of artemisinin and its various derivatives (dihydroartemisinin, dihydroartemisinin 12-benzoate, 12-(2′-hydroxyethyl) deoxoartemisinin, 12-(2′-ethylthio) deoxoartemisinin dimer, deoxoartemisinin trimer) in comparison with paclitaxel (Taxol), 5-fluorouracil (5-FU), cisplatin in vitro.</P><B>Results.</B><P>In this study, the deoxoartemisinin trimer had the most potent antitumor effect (IC<SUB>50</SUB> = 6.0 μM), even better than paclitaxel (IC<SUB>50</SUB> = 13.1 μM), on oral cancer cell line (YD-10B). In addition, it induced apoptosis through a caspase-3-dependent mechanism.</P><B>Conclusion.</B><P>The deoxoartemisinin trimer was found to have greater antitumor effect on tumor cells than other commonly used chemotherapeutic drugs, such as 5-FU, cisplatin, and paclitaxel. Furthermore, the ability of artemisinin and its derivatives to induce apoptosis highlights their potential as chemotherapeutic agents, for many anticancer drugs achieve their antitumor effects by inducing apoptosis in tumor cells. © 2006 Wiley Periodicals, Inc. Head Neck, 2007.</P>

Polyoxygenated Flavones; Synthesis, Cytotoxicities and Antitumor Activity against ICR Mice Carrying S-180 Cells

Song, Gyu-Yong,Ahn, Byung-Zun The Pharmaceutical Society of Korea 1995 Archives of Pharmacal Research Vol.18 No.6

Fitty two flavones were synthesized from polyoxygenated dibenzoylmethanes which were obtained by a modified Baker-Venkatarman rearrangement, of 2-benzoyl oxyacetophenones. The following flavones among them showed good cytotoxic activities against L1210 and HL60 cells ; 2'-benzoyloxy-5,7-dimethoxyflavone $(8.2{\mu}g/ml,{\;}5.0 {\mu}g/ml)$, 2'-benzyloxy-5,7,8-trimethoxyflavone $(5,9 {\mu}g/ml,{\;}11.0{\mu}g/ml,{\;}2.7{\mu}g/ml)$, 2'-hydroxy-5,7,8-trimethoxyflavone $(9.8{\mu}/ml,{\;}6.2{\mu}g/ml)$, 2'-benzyloxy-5-hydroxyflavone $(5.2 {\mu}g/ml,{\;}3.6{\mu}g/ml)$, and 5,2'-dihydroxyflavone $(5.1{\mu}g/ml,{\;}4.0{\mu}g/ml)$. Presence of 5-methoxy group potentiated the cytotoxic activity, while the existence of 7-methoxy group decreased the activity. 5-Hydroxy or methoxy activates 4-carbonyl group, while 7-methoxy group deactivates the acrbonyl group. From these observation it was concluded that the activation of carbonyl group at C-4 of a flavone is important for the enahncement of the cytotoxic activity. The presence of both 5-hydroxy and 2-benzyloxy-or 2-hydroxy group enhanced the antitumor activity; 2'-benzyloxy-5-hydroxy-7-methoxyflaone 9T/C=144%), 5.2'-dihydroxy-7-methoxyflavone (T/C=132%) and 5,2'-dihydroxy-6,78,6' trtramethoxyflvone (T/C = 172%) 2'hexanolytion of 5,2'-dihydroxy-flavones did not improve the natitumor activity; 2' hexanoyloxy-5-hydroxy-7-methoxyflavone showed T/C = 132%, about the same as that of 5,2'-dihydroxy-7-methoxyflvone (T/C=130%)