• Bulletin of the Korean Chemical Society
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• v.35 no.1
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• pp.129-134
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• 2014

Two series of SAHA-liked hydroxamate analogues were designed, synthesized and evaluated for their biological activities against nuclear HDACs. Compounds of Series I were found to be very effective inhibitors of cancer cell growth in the PC-3, Hut78, K562 and Jurkat E6-1 cancer cell lines with mean $IC_{50}$ values from $0.54{\mu}M$ (Ic, Jurkat E6-1) to $7.73{\mu}M$ (Ib, K562), indicating that they are cell permeable and the benzimidazolyl-based ligands are flexible enough to occupy the binding site of HDAC.

• Applied Biological Chemistry
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• v.51 no.2
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• pp.124-128
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• 2008

Cell proliferation inhibitory effects of homoharringtonine (HHT), an active drug substance in Cephalotaxus koreana, against blood cancer cell line K562 were evaluated. In addition, in vivo chronic toxicity test with mouse was carried out. When K562 cell line was treated everyday for 9, 6, 3 days, $IC_{50}$ values of HHT were determined as 0.27, 0.37, and 1.10 mM respectively. The anticancer activity of HHT was comparable to adriamycin, a known anticancer drug compound for blood cancer treatment. in vivo chronic toxicity test of the HHT, the number of red blood cell (RBC) showed no significant difference. From the analysis of the liver-functional enzymes in blood, all of liver damage related enzymes such as glutamate-oxalate-transferase (GOT), glutamate-pyruvate-transferase (GPT), cholesterol (Chol) and alkaline phosphatase (ALP) showed no significant change. However, from the histologic test, a neutrophil of the band type in liver tissue was observed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5659-5665
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• 2014

Background: To investigate the antioxidant value and anticancer functions of mitragynine (MTG) and its silane-reduced analogues (SRM) in vitro. Materials and Methods: MTG and SRM was analyzed for their reducing power ability, ABTS radical inhibition and 1,1-diphenyl-2-picryl hydrazylfree radicals scavenging activities. Furthermore, the antiproliferation efficacy was evaluated using MTT assay on K 562 and HCT116 cancer cell lines versus NIH/3T3 and CCD18-Co normal cell lines respectively. Results: SRM and MTG demonstrate moderate antioxidant value with ABTS assay (Trolox equivalent antioxidant capacity (TEAC): $2.25{\pm}0.02$ mmol trolox / mmol and $1.96{\pm}0.04$ mmol trolox / mmol respectively) and DPPH ($IC_{50}=3.75{\pm}0.04mg/mL$ and $IC_{50}=2.28{\pm}0.02mg/mL$ respectively). Both MTG and SRM demonstrate equal potency ($IC_{50}=25.20{\pm}1.53$ and $IC_{50}=22.19{\pm}1.06$ respectively) towards K 562 cell lines, comparable to control, betulinic acid (BA) ($IC_{50}24.40{\pm}1.26$). Both compounds showed concentration-dependent cytototoxicity effects and exert profound antiproliferative efficacy at concentration > $100{\mu}M$ towards HCT 116 and K 562 cancer cell lines, comparable to those of BA and 5-FU (5-Fluorouracil). Furthermore, both MTG and SRM exhibit high selectivity towards HCT 116 cell lines with selective indexes of 3.14 and 2.93 respectively compared to 5-FU (SI=0.60). Conclusions: These findings revealed that the medicinal and nutitional values of mitragynine obtained from ketum leaves that growth in tropical forest of Southeast Asia and its analogues does not limited to analgesic properties but could be promising antioxidant and anticancer or chemopreventive compounds.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7055-7059
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• 2014

Artemisia, as one of the largest genera in the tribe Anthemideae of the Asteraceae comprises an important part of Iranian flora. While cytotoxic and apoptotic properties have already been reported for some species of the genus there is not any report on cytotoxic effects of A. ciniformis. Petroleum ether (40-60), dichloromethane, ethyl acetate, ethanol and ethanol-water (50:50) extracts of the aerial parts of A. cinformis were subjected to cytotoxic and apoptotic evaluations on two cancer human cell lines (K562 and HL-60) and on J774 normal cells. Among multiple extracts evaluated for cytotoxicity, dichloromethane ($CH_2Cl_2$) and petroleum ether (PE) extracts were shown to possess the highest anti-proliferative effects on HL-60 and K562 cells with $IC_{50}$ values of 31.3 and $25.5{\mu}g/ml$ respectively. Apoptosis induction verified by sub-G1 peaks was seen in flow cytometry histograms. Increase in the amount of Bax protein, formation of DNA fragments, and cleavage of PARP to 24 and 89kDa sub units all confirmed induction of apoptosis by A. cinformis extracts. Taken together according to the result of the present study some extracts of A. cinformis could be considered as sources for natural cytotoxic compounds and further mechanistic and phytochemical studies are recommended to fully understand the underlying mechanisms of cnacer cell death as well as identification of responsible phytochemicals.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4773-4780
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• 2014

Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment. Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusion protein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the five candidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations ($IC_{50}$) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6 nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes of apoptosis such as shrunken, fragmentation nucleus as well as "apoptotic bodies" after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.

• Microbiology and Biotechnology Letters
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• v.21 no.1
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• pp.59-65
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• 1993

We isolated Actinomycetes strain GMT 1155 and purified the active compound, MT 1155, on the morphological reversion of ts/NRK cell from the isolate. MT 1155 was identified as toyocamycin having antifungal and antitumor activities from physico-chemical properties and UV, IR, $^1H$-NMR, $^13C$-NMR and mass spectrum. MT 1155 showed the morphologically reversional activity on ts/NRK cell and the cytotoxicity on CTLL cell at the final concentrations of 1.7 JlM and 0.2 11M, respectively and its $IC_{50}$ value on protein kinase A enzyme was 2.3 $\mu$M. Also it had strong antifungal activity against several pathogenic fungi but not antibacterial activity. And it did not inhibit both protein kinase C activity and the bleb-formation of K562 cell induced by phorbol esters.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.12 no.1
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• pp.79-98
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• 1999

The purpose of this Study was to investigate effect of TakliSodokSan(TSS) on the anti-tumor, immunocytes and nitric oxide(NO) production from mice peritoneal macrophages. This Study estimated the proliferation of L1210 cell lines, A431 cell lines, Hep-G2 cell lines, K562 cell lines, 3T3 cell lines, mouse thymocytes and mouse splenocytes and NO production from pcritoneal macrophages in vitro, and estimated the proliferation of L1210 cells, thymocytes and splenocytcs, NO production from peritoneal macrophages and body weight in L1210 cells-transplanted mice in vivo. The results were obtained as follows; 1. TSS inhibited significantly the proliferation of L1210, A431, Hep-G2, K562 cell lines in vitro. 2. TSS accelerated the proliferation of mice thymocytes and splenocytes in vitro. 3. TSS was not increased the nitric oxide production from mice peritoneal macrophages in vitro. 4. TSS inhibited significantly the proliferation of L1210 cells in Ll210 cells∼transplanted mice. 5. TSS accelerated the proliferation of mice thymocytes and splenocytes In L1210 cells-transplanted mice. 6. TSS was increased significantly the nitric oxide production from mice peritoneal macrophages in L1210 cells-transplanted mice. 7. TSS was increased the body weight as comparing with control group in Ll210 cells-transplanted mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.913-921
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• 2005

In this study, we investigated gene expression patterns induced by Ailanthus altissima extract and compared it with Gleevec, a well-known anti-leukemia drug, in K562 chromic leukemia cells. Ailanthus altissima extract(100 ug/ml) and Gleevec(50 ug/ml) were treated to cells for 1h, 2h, 4h, and 16h and total RNA was extracted. Gene expressions were evaluated using cDMA microarray, in which 24,000 genes were spotted. Hierarchical clustering analysis showed that expression of genes included in two clusters were increased or decreased time dependently by both Ailanthus altissima extract and Gleevec. Genes included in another cluster were induced by Ailanthus altissima extract but not by Gleevec. In biological process analysis, expression of genes involved in apoptosis, growth arrest and DNA-damage were increased, but genes stimulating cell cycle were decreased. This study provides comprehensive comparison of the patterns of gene expression changes induced by Ailanthus altissima extract and Gleevec in K-562 leukemia cells.

• Polymer Science and Technology
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• v.21 no.6
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• pp.557-562
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• 2010

• Archives of Pharmacal Research
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• v.20 no.4
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• pp.342-345
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• 1997

A cytotoxic constituent was isolated by bioassay-guided procedure from the roots of Sophora flavescens Aiton (Leguminosae). The constituent was identified as sophoraflavanone G (I) by means of chemical methods and in comparsion with spectral data of standard compound. The $ED_50$ values of constituent I were 0.78, 1.57, 2.14 and $8.59{\mu}g/ml$ against A549, HeLa, K562 and L1210 cell lines, respectively. Constituent I exhibited highly cytotoxic activities against A549, K562 and HeLa cells, but showed a mild activity $$(ED_50 value, 5{\mu}g/ml)$$ against L1210 cells. Among the tested cell lines, A549 cells were the most sensitive to constituent I.