• Archives of Pharmacal Research
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• 제18권6호
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• pp.396-401
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• 1995

As a part of trials to develop the antitumor agent from tannins isolated from plants, the antitumor activity of peduculagin, an ellagitannin, isolated from Alnus hirsuta var. microphylla was examined in vitro and in vivo. In vitro, the cytotoxicity was determined by 0.4% typanblue dye exclusion method. peduculagin showed the dose-dependent cytotoxicity against human chronic myelogenous leukemia (K-562), human promyelocytic leukemia (HL-60), mouse lymphoid neoplasm (P388), mouse lymphocytic leukemia (L1210) and mouse sarcoma 180(S180) cell lines. $ED_{50}\; values\; (ED_{50})$ of each cell line were 5.30, 0.92, 2.78, 9.35 and $1.38 \mug/ml$ respectively. The most sensitive cell line was HL-60. In vivo, pedunculagin was administered to ICR mouse with the doses of 50 and $100{\;}{\mu}g/ml$intraperitoneally once at 20 days before S180 inoculation. peduculagin showed the antitumor activity and its T/C ratio (%) was 120.82% in the group of both concentrations.

• Toxicological Research
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• 제13권4호
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• pp.311-316
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• 1997

This study was carried out to develop antitumor effect of the n-butanol soluble fraction of Perilla frutescens on (KB cells) human oral epitheloid carcinoma cells. The cytotoxictty of methanollc extract of Perilla frutescens on KB cells was evaluated by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide(MTT) assay. The antitumor activity of various fractions obtained from n-butanol soluble fraction of Perilla frutescens was evaluated in human oral epithelold carcinoma cells. The antitumor acavity of the n-butanol soluble fraction on human oral epitheloid carcinoma cells was evaluated by MTT assay of colorimetric method. The light microscopic study was carried out to observe morphological changes of cultured human oral epitheloid carcinoma cells. These results were obtained as follows; 1. The fractions 1,2 and 3 of the n-butanol soluble fraction of Perilla frutescens were shown significant antitumor activities. 2. The number of human oral epitheloid carcinoma cells were decreased and tend to form cell cluster by treatment with fractions 1,2,3 and 4 of the n-butanol soluble fraction of Perilla frutescens. 3. The fraction 1 of the n-butanol soluble fraction of Perllla frutescens showed the highest antitumor activity on Perilla frutescens. It has been selected as a lead fraction for further examinations.

• Journal of Ginseng Research
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• 제46권6호
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• pp.738-749
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• 2022

Background: Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20(R)-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20(R)-panaxotriol and investigate its antitumor activity in vivo and in vitro. Methods: Here, 20(R)-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by ¹H-NMR, ¹³C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay. Results: The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2H-pyran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl(tert-butoxycarbonyl)glycinate (A11). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC₅₀ < 0.3 µM) was more than 100 times higher than that of 20(R)- panaxotriol (IC₅₀ > 30 µM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20(R)-panaxotriol (p < 0.01) in vivo. Conclusion: To our knowledge, this is the first study to report the production of derivative A11 from 20(R)-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.

• 약학회지
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• 제44권4호
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• pp.347-353
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• 2000

To examine influence of artificial digestive juice on the antitumor activity of Ganoderma lucidum-A(GL-A), protein-bound polysaccharide from Ganoderma lucidum, we compared the digested protein-bound polysaccharide with undigested one both on immunopotentiating activity and influence of digestive juices. Protein-bound polysaccharide GL-B was obtained by digesting the antitumor component GL-A with artificial digestive Juices in vitro. When GL-A was administered orally to sarcoma 180 tumor-bearing ICR mice, the life prolonging effect was exhibited in a dose dependent manner Not only GL-A but GL-B increased the production of colony forming unit (CFU) to 10- and 8-fold of that of the control, respectively. Both of the protein-bound polysaccharides also showed the secretion of nitric oxide in RAW 264.7 cell lines to 3.5-and 3.7-fold of that of the control, respectively: GL-A activated components of the alternative complement pathway, whereas GL-B did not. In humoral immunity GL-A increased the activity of alkaline phosphatase in differentiated B cells to 3 times and GL-B to 4 times of that of the control. These results showed that the artificial digestive juices had no influence on the antitumor activity of the protein-bound polysaccharide from Ganoderma lucidum and that its immunomodulating activity retained after treatment with artificial digestive juice. And this provides a basis of the protein-bound polysaccharide of Ganoderma lucidum as an peroral anticancer drug.

• Biomolecules & Therapeutics
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• 제8권3호
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• pp.235-240
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• 2000

Antitumor effect of LC43, a protein-bound ploysaccharide (M.W. 43 kDa) that was purified from intergeneric protoplast fusant of Lentinus edodes and Coriolus versicolor, was elucidated against mouse sarcoma 180 cell in vitro and in vivo. By injecting LC43 into ICR mice bearing solid or ascitic sarcoma 180, tumor regression and survival rates were investigated. To examine the effects of LC43 on immunopotentiation activity. immunoorgan weight, B cell differentiation, T cell activity and macrophage activation were determined. LC43 showed antitumor effects against both solid tumor and ascitic tumor of sarcoma 180. It did not change significantly the immunoorgan weight but potentiated immune responses such as B cell differentiation and the release of superoxide anion from macrophages. These results suggest that the protein-bound polysaccharide of LC43 exhibited antitumor activities through the activation of immune-related cells and acted as an immunmodulator.

• Archives of Pharmacal Research
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• 제21권4호
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• pp.445-451
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• 1998

A series of 5-hydroxy-4-quinolone (3) and 5-methoxy-4-quinolone (4) derivatives were synthesized as truncated acridone analogues and evaluated for antitumor, antiheroes and antituberculosis activities. Among them 5-hydroxy-8-methoxy-quinolone showed potent antitumor activity ($IC_{50}$=17.7 $\mu\textrm{M}$ for HL60) which was greater than that of acronycine. However, these compounds didn't show any significant antiheroes or antituberculosis activity.

• Journal of Microbiology and Biotechnology
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• 제12권3호
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• pp.503-507
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• 2002

Chitosan oligosaccharides (COSs) were prepared and fractionated into three groups of COS [a high molecular weight COS (HMWCOS), medium molecular weight COS (LMWCOS), and low molecular weight COS (LMWCOS)] according to their molecular weight, using an ultrafiltration membrane enzymatic bioreactor designed earlier [8]. Antitumor activity of these COSs was then examined against Sarcoma 180 solid (S180) or Uterine cervix carcinoma No. 14 (Ul4) tumor cell-bearing mice. Among these COSs, MMWCOS with molecular weight range from 1.5 to 5.5 kDa effectively inhibited the growth of both tumor cells in the mice. In addition, the administration of MMWCOS resulted in increased thymus weight among lymphoid organs. The mice treated with MMWCOS showed improved survival rate and larger number of survivors after 40 days of feeding. The most effective of MMWCOS far antitumor activity in the S180- or U14-bearing mice was 20 mg/kg/day or more.

• Archives of Pharmacal Research
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• 제22권6호
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• pp.592-607
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• 1999

2-(1-Aryl-1-hydroxymethyl)-and 2-aroyl-DHAQ derivatives (DHAQ, 1,4-dihydroxy-,10-anthraquinone), and 2-(1-aryl-1-hydroxymethyl)-ATO derivatives (ATO, anthraceneactivity (T/C 125~128%), though their cytotoxicity was not further improved compared to that of 2-(1-aryl-1-dydroxymethyl)-1,4-dihydroxy-9,10-anthraquinones. They manifested no correlation between the cytotoxicity and the antitumor activity. In case of 2-[1-hydroxy-1-(4-propylphenyl)-methyl]-ATO, the most bioactive one in viv-1,4,9,10-tetraone) were synthesized and their antitumor activities were determined. 2-(1-Aryl-1-hydroxymethyl)-DHAQ derivatives showed a stronger cytotoxicity compared to the series of 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinone derivatives. It was suggested that the presence of aryl group at the side chain accelerated the bioreductive activation leading to cell death. 2-Aroyl-DHAQ derivatives, despite their higher electrophilicity, revealed smaller cytotoxicity and antitumor activity (expressed by T/C value) than 2-(1-aryl-1-hydroxymethyl)-DHAQ derivatives. Thus, no consistent relationship between the electronic effect on aromatic side chain and the cytotoxicity was observed. ATO series exhibited a higher antitumor o among the same series, it showed an $ED_{50}$ value of 10.2 mg/mL and a T/C value of 218%. It is assumed that the anthrancene1,4,9,10-tetraones after uptake into cellular tissues might be transformed to a cytotoxic metabolite(s).

• Archives of Pharmacal Research
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• 제21권2호
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• pp.193-197
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• 1998

A number of substituted isoquinolin-1-ones, possible bioisosteres of the 5-aryl substituted 2,3-dihydroimidazo[2,$1-a$]isoquinolines, were synthesized and tested for their antitumor activity against five different human tumor cell lines. O-(3-hydroxyporpyl) substituted compound (15) exhibited the best antitumor activity which is 3-5 times better than 5-[$4^1$-(piperidinomethyl)phenyl]-2,3-dihydroimidazo[2,$1-a$]isoquinoline (1).

• 생약학회지
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• 제35권3호통권138호
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• pp.199-202
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• 2004

A highly potent antitumor sesquiterpene O-naphthoquionone has been isolated from Ulmus davidiana, which has been traditionally used as the folk medicine. The structure of this compound was established on the basis of spectral data obtained from UV, IR, MS, and NMR spectrometry, and determined as mansonone E. This compound showed potent antitumor activity on in vivo assay, hollow fiber and xenograft assay.