• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.7
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• pp.819-824
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• 2007

The present study describes the cytotoxic effect of Artemisia fukudo extracts. The extract from A. fukudo by 80% ethanol was fractionated with n-hexane, dichloromethane, ethylacetate, and butanol in serial. The cytotoxicity of A. fukudo extracts was examined for its effect on the growth of HL-60 cells by the colorimetric 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, we used the HL-60 cells to see what effects the A. fukudo extracts will have on apoptosis of cancer cells. We checked the cell activity, cell morphologic changes, DNA fragmentation, and DNA content after 24 hr incubation with administering 25 ${\mu}g/mL$ of the A. fukudo extracts. In the treatment of the low concentration of n-hexane and dichloromethane fractions, the survival rate of HL-60 cells is lower than that of the control. The laddering-pattern DNA fragmentation was observed in the treatment with n-hexane and dichloromethane fractions. The DNA content of the cells apoptosis measured as the density of sub-$G_{1}$ hypodiploid cells by flow cytometric analysis. The number of sub-$G_{1}$ hypodiploid cells increased in the treatment with n-hexane and dichloromethane fractions. These fractions obstructed the cell cohesion and caused the blebbing of the cell membrane and fragmentation of the nucleus, both of which are symptoms of apoptosis. These results suggest that A. fukudo has a great potential value as food additives, medicinal supplements for patients with chronic diseases, and preventive measures against cancer.

• Journal of Food Hygiene and Safety
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• v.21 no.3
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• pp.171-180
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• 2006

Peroxisome proliferatorr-activated receptor-gamma $(PPAR{\gamma})$ must form a heterodimer with the retinoid-X receptor (RXR) to bind DNA, and its transcriptional activity is thought to be maximized by ligands specific for either receptor. Activated $(PPAR{\gamma})$ and $(PPAR{\gamma})$ ligands may influence tumor growth through regulation of the tumor suppressor PTEN. Our aim in this study was to determine whether co-stimulation with the $(PPAR{\gamma})$ ligand, ciglitazone, and RXR ligand can synergistically upregulate PTEN in human acute promyelocytic leukemia (APL) cells and consequently potentate the inhibition of cell growth and cell cycle progression of these cells. Human leukemia cell line, HL-60 cells were exposed to all-trans-retinol and ciglutazone. The PTEN expression was measured as the level of PTEN mRNA expression by RT-PCR and as the level of PTEN expression by western blot analysis. Cell cycle analysis was carried out by a propidium iodide (PI) staining method and analyzed with a FACScan. The $(PPAR{\gamma})$ ligand, ciglitazone, and the RXR ligand, retinoic acid, upregulated PTEN expression by HL-60 cells in time- and dose-dependent manners, respectively. This was significantly enhanced by a combination of both ciglitazone and retinoic acid. Moreover, these compounds synergistically induced arrests of both cell growth and the $G_l$ phase of the cell cycle. Thus, the activation of the $(PPAR{\gamma})$:RXR heterodimer may represent a regulatory pathway for human leukemia cells and there may be important roles for $(PPAR{\gamma})$ and RXR ligands in prophylactic and therapeutic approaches fur controlling leukemia through the upregulation of PTEN.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7053-7060
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• 2015

In the present work, novel orange peel was extracted with 100%EtOH (ethanol) and fractionated into four fractions namely F1, F2, F3, F4 which were eluted from paper chromatographs using 100%EtOH, 80%EtOH, 50%EtOH and pure water respectively. The crude extract and its four fractions were evaluated for their total polyphenol content (TPC), total flavonoid content (TFC) and radical scavenging activity using DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Their cytotoxic activity using WST assay and DNA damage by agarose gel electrophoresis were also evaluated in a human leukemia HL-60 cell line. The findings revealed that F4 had the highest TPC followed by crude extract, F2, F3 and F1. However, the crude extract had the highest TFC followed by F4, F3, F2, and F1. Depending on the values of $EC_{50}$ and trolox equivalent antioxidant capacity, F4 possessed the strongest antioxidant activity while F1 and F2 displayed weak antioxidant activity. Further, incubation HL-60 cells with extract/fractions for 24h caused an inhibition of cell viability in a concentration-dependent manner. F3 and F4 exhibited a high antiproliferative activity with a narrow range of $IC_{50}$ values ($45.9-48.9{\mu}g/ml$). Crude extract exhibited the weakest antiproliferative activity with an $IC_{50}$ value of $314.89{\mu}g/ml$. Analysis of DNA fragmentation displayed DNA degradation in the form of a smear-type pattern upon agarose gel after incubation of HL-60 cells with F3 and F4 for 6 h. Overall, F3 and F4 appear to be good sources of phytochemicals with antioxidant and potential anticancer activities.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1028-1035
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• 2004

Imperatorin, a biologically active furanocoumarin from the roots of Angelica dahurica (Umbelliferae), was mutagenic and induced transformation of mouse fibroblast cell lines, whereas it provided inhibiting effects on mutagenesis and carcinogenesis induced by various carcinogens. Furthermore, it has been suggested that imperatorin may have potential anticarcinogenic effects when administered orally in the diet. In addition to its anticarcinogenic properties, imperatorin has been shown to possess anticancer activities. We investigated the macro scale gene expression analysis on the HL-60 cells treated with imperatorin. Imperatorin (10μM) were used to treat the cells for 6h, 12h, 24h, 48h, and 72h. In a human cDNAchip study of 10,000 genes evaluated 6, 12, 24, 48, 72 hours after treated with imperatorin in HL-60 cells. Hierarchical cluster against the genes which showed expression changes by more than 2 fold. Three hundred eighty six genes were grouped into 6 clusters by a hierarchical clustering algorithm. Pathway analysis using gene microarray pathway prof Her that is a computer application designed to visualize gene expression data on screen representing biological pathways and groupings of genes.

• Preventive Nutrition and Food Science
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• v.8 no.2
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• pp.113-118
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• 2003

We recently extracted lignans such as matairesinol and 2-hydroxyarctigenin from safflower seeds and found that they exhibit a potent cytotoxic effect on human promyleocytic leukemia HL-60 cells. In this study, we investigated whether mechanisms of the matairesinol-induced cell death are associated with the programmed cell death, apoptosis. Matairesinol dose-dependently reduced viability of HL-60 cells with an IC/sun 50/ value of 60 $\mu$M. Staining of cells with Hoechst 33342 revealed distinct morphological features of apoptosis, such as the nuclei broken into chromatin containing fragments of various sizes in the cells exposed to 100 $\mu$M matairesinol for 24 hr. Agarose gel electrophoresis of DNA from the cells treated with matairesinol showed internucleosomal DNA degradation into oligonucleosomal sizes. DNA ladder like patterns were easily detected after treatment with matairesinol concentrations ranging from 10 to 100 $\mu$M after 24 hr. In cells treated with 100 $\mu$M matairesinol for differing time periods, the DNA ladder was detectable from 6 hr onward. A time course histogram of the DNA content analyzed by flow cytometry revealed a rapid increase in subdiploid cells and a concomitant decrease in diploid cells exposed to 100 $\mu$M matairesinol. These results indicate that matairesinol-induced HL-60 cell death was due to the DNA damage and apoptosis.

• Journal of Radiation Industry
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• v.4 no.1
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• pp.91-94
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• 2010

A number of epidemiological studies as well as biological experiments, showed that genistein, one of the isoflavone, prevents prostate cancer occurrence. In this study, we showed that genistein inhibited the cell proliferation of human promyeoltic leukemia HL-60 cells and induced G2/M phase arrest. In addition, combination of genistein treatment and ${\gamma}$-irradiation displayed synergistic effect in apoptotic cell death of HL-60 cells. This means that the repair of genistein-induced DNA damage was hindered by ${\gamma}$-radiation and thus cell death was increased. In conclusion, genistein is one of the important chemicals that sensitize radiation-induced cell death.

• Food Science and Biotechnology
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• v.17 no.1
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• pp.188-190
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• 2008

In east Asia, the leaves of various Sasa species have been used in folk medicine for centuries. The effects of the methanolic extract and its subsequent fractions derived from the leaves of Sasa quelpaertensis Nakai on cell proliferation in human leukemia HL-60 cells were evaluated. The ethyl acetate fraction of this extract (ESQL) significantly reduced cell viability in a dose-dependent manner ($0-250\;{\mu}g/mL$). ESQL ($IC_{50}=24.8\;{\mu}g/mL$) exhibited growth inhibition comparable to the main constituent of green tea, epigallocatechin ($IC_{50}=26.2\;{\mu}g/mL$), which was used as a positive control. ESQL treatment induced apoptosis, which was confirmed by the presence of nuclear condensation and annexin V-staining. These results demonstrate that ESQL contains chemopreventive phytochemicals that may be useful in neutraceutical applications.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.327-331
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• 2002

The purpose of this research was to investigate the immuno-modulatory effect and anti-carcinogenic property of Cordyceps militaris(CM) and/or Paecilomyces japonicus (PJ). The proliferation of cultured splenocytes and thymocytes were enhanced by the addition of 10 ㎍/ml of CM and/or PJ. B lymphocytes subpopulation in splenocytes were increased both CM and/or PJ administered(p.o. for 7 days)-mice. Thymic T lymphocytes, especially TH cells were significantly increased in CM-administered mice. CM and/or PJ treatment inhibited the cell viability of L 1210 mouse leukemia and HL60 human leukemia cells and induced the apoptosis of L1210 and HL60 cells. In addition, CM and/or PJ increased the hemaggutination(HA) titer against SRBC. These results suggest that CM and/or PJ have an immuno-modulatory action and anti-carcinogenic property.

• Bulletin of the Korean Chemical Society
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• v.34 no.5
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• pp.1349-1354
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• 2013

Twenty two new 5-fluorouracil (5-FU) derivatives, 2-butoxy-4-substituted 5-fluoropyrimidines, were synthesized and characterized by IR, $^1H$ NMR, MS, HRMS. All compounds were preliminarily evaluated by MTT assay on human liver BEL-7402 cancer cell line in vitro. Ten compounds were selected to test their cytotoxic activity against A549, HL-60 and MCF-7 cancer cell lines in vitro. These compounds were more sensitive to BEL-7402 than other cell lines, particularly, cytotoxic activity of compounds 6b, 6d-f, 6p, 6s-u were in sub-micromolar scale. The highest cytotoxic potency against A549, HL-60 and MCF-7 was shown by 2-butoxy-4-chloro-5-fluoropyrimidine (5) with $IC_{50}$ values of 0.10, 1.66 and $0.59{\mu}M$, respectively. Compounds 6d and 6e were effective against MCF-7 with $IC_{50}$ $9.73{\mu}M$ and HL-60 with $IC_{50}$ $8.83{\mu}M$, respectively.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1370-1374
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• 2005

The Tosyl-JM3 (TJM3) is a modified compound from one of 1,2,3,4-Tetra- hydroisoquinoline (THIQ) derivatives. The THIQs include potent cytotoxic agents that display a range of anti-tumor activities, antimicrobial activity, and other biological properties. In this study, we investigated the effect of TJM3 on the cytotoxicity, induction of apoptosis in human promyelocytic leukemia cells (HL-60 cells). TJM3 showed a significant cytotoxic activity in HL-60 cells (IC50 = approximately $60{\mu}g/m{\ell}$) after a 24 hr incubation. Treatment of HL-60 cells with TJM3 exhibited several features of apoptosis, including formation of DNA ladders in agarose gel electrophoresis, morphological changes of HL-60 cells with DAPI stain. Here we observed that TJM3 caused a decrease of procaspase-3 protein. Further molecular analysis demonstrated that TJM3 led to cleavage of poly(ADP-ribose) polymerase (PARP) by western blot and increase of hypodiploid (Sub-G1) population in the flow cytometric analysis. In conclusion, these above results indicate that TJM3 dramatically suppresses HL-60 cell growth and induces apoptosis. These data may support a possibility for the use of TJM3 in the prevention and treatment of leukemia.