• Toxicological Research
• /
• v.19 no.3
• /
• pp.197-203
• /
• 2003

Apicidin, a histone-deacetylase inhibitor, has been successfully used to inhibit the growth of cancer cells. In this study, the apoptotic potential and mechanistic insights of apicidin were investigated in human myeloid leukemia U937 cells. Treatment of U937 cells with apicidin resulted in a decrease of cell viability with apoptotic characteristics, including chromatin condensation and ladder-pattern fragmentation of genomic DNA. Apicidin converted the procaspase-3 protease to catalytically active effector protease, resulting in subsequent cleavage of poly (ADP-ribose) polymerase (PARP) and inhibitor of caspase-activated deoxyribonuclease (ICAD). In addition, apicidin induced the activation of caspase-9 protease and the cytosolic release of mitochondrial cytochrome c with mitochon-drial membrane potential transition. Moreover, apicidin transiently increased the expression of Fas and Fas ligand proteins. Taken together, the results suggest that apicidin induces apoptosis of U937 cells through activation of intrinsic caspase cascades and Fas/FasL system with mitochondrial dysfunction.

• Environmental Mutagens and Carcinogens
• /
• v.22 no.3
• /
• pp.205-210
• /
• 2002

In irradiated human lymphocytes, translocation of chromosome has been more frequently observed than dicentric chromosome. Differences in the misrepair process leading to translocation and dicentric chromosomes may explain the above observations. In order to find out whether dicentric and translocation are originated from different mechanism, the frequencies of radiation induced translocation and dicentric in lymphocytes were examined following treatment of irradiated lymphocytes with two DNA repair inhibitors, 3AB for inhibition of poly(ADP-ribose) synthesis and Ara C for inhibition of DNA-polymerase $\alpha$. Ara C potentiated the frequencies of radiation induced dicentric and translocation. 3AB also potentiated the frequencies of radiation induced dicentric, but not translocation. These results suggest the potential differences in the mechanisms in the formation of translocation and dicentric chromosomes.

• Biomedical Science Letters
• /
• v.15 no.2
• /
• pp.147-152
• /
• 2009

Lycopus lucid us Turcz is well known as traditional Chinese medicine, and it has been shown to exhibit antiinflammatory, -allergic and -oxidative effect. However, its anti-cancer properties have not been examined yet. In this study, we investigated the effect of the methanol extract of Lycopus lucid us Turcz on anti-cancer effect in MCF-7 human breast cancer cells. Treatment of Lycopus lucidus Turcz extract induced apoptosis and inhibition of cell proliferation in dose- and time-dependent manner. Apoptosis in the MCF-7 cells was characterized with the changes in nuclear morphology; decrease of Bcl-2 and caspase-7 expression; and increase of cleaved poly ADP-ribose polymerase(PARP). Furthermore, treatment of Lycopus lucidus Turcz extract caused the down-regulation of cell cycle-related protein including, cdk4, cyclin D1 and E2F-1. These results suggest that Lycopus lucidus Turcz might have the therapeutic value against human breast cancer cells.

• Environmental Mutagens and Carcinogens
• /
• v.11 no.2
• /
• pp.107-117
• /
• 1991

The effect of 3-aminobenzamide (3AB), an inhibitor of poly (ADP-ribose) polymerase, on ethyl methanesulfonate (EMS)-or bleomycin (BLM)-induced DNA repair synthesis and chromosome aberrations was examined during the cell cycle of Chinese hamster ovary (CHO)-K$_1$ cells. The synchronized cells were obtained by using thymidine double block method and mitotic selection method. Three assays were employed in this study: unscheduled DNA synthesis, alkaline elution and chromosome aberrations. 3AB alone did not induce DNA repair and chromosome aberrations in all phases. The post-treatment with 3AB inhibited DNA repair synthesis induced by EMS or BLM in G$_2$ phase, whereas 3AB did not affect chromosome aberrations induced by EMS or BLM in all phases. These results suggest that 3AB aggravates the cell cycle disturbance which occur after DNA damage, and leads to an accumulation of cells at G$_2$ phase, and inhibits DNA repair synthesis, while the effect 3AB on chromosome aberrations may need reevaluated.

• The Journal of Korean Medicine
• /
• v.25 no.2
• /
• pp.184-193
• /
• 2004

Objectives: This study was designed to investigate effects of Gwibitang on the glutamate-induced toxicity of primary rat neonatal astrocytes. Methods and Results: Gwibitang significantly recovered the glutamate-induced apoptosis and inhibited the generation of $H_2O_2$ in astrocytes. In addition, both Gwibitang and antioxidants such as GSH reduced the glutamate-induced cytotoxicity in astrocytes, indicating that Gwibitang possibly had an antioxidative effect. Moreover, Gwibitang also inhibited the glutamate-induced degradation of Bcl-2 protein and poly(ADP)-ribose polymerase (PARP) in astrocytes. Conclusions: We suggest that Gwibitang has protective effects on glutamate-induced cytotoxicity via an antioxidative mechanism.

• Journal of Microbiology and Biotechnology
• /
• v.19 no.3
• /
• pp.286-290
• /
• 2009

In the course of screening for substances inhibiting apoptosis of U937 human leukemia cells induced by etoposide ($10\;{\mu}g/ml$), Forsythiae fructus, which showed a high level of inhibition, was selected. The regulating compounds were purified from the ethyl acetate extract by silica gel column chromatography and HPLC. The active substance was purified and identified as rengyolone by spectroscopic methods. This compound showed inhibitory activity on caspase-3 induction, a major protease of the apoptosis cascade, with an $IC_{50}$ value of $38.96\;{\mu}M$ after 8 h of etoposide treatment in U937 cells. The expression level of caspase-3 and poly(ADP-ribose) polymerase (PARP) were dose-dependently inhibited by the compound, suggesting that rengyolone inhibits etoposide-induced apoptosis via downregulation of caspases.

• Journal of Nutrition and Health
• /
• v.36 no.8
• /
• pp.828-833
• /
• 2003

Dially disulfide (DADS), a component of garlic (Allium sativum), has been known to exert potent chemopreventive activity against various cancers. In this study, the synergistic effect of DADS and daunorubicin on the cytotoxicity of HL-60 cells, a human leukemia cell line, was investigated. DADS at 25 M greatly potentiated daunorubicin-induced cell death, decreasing cell viabilityto50%ofthe control. Daunorubicin-induced apoptosis was accompanied by the activation of caspase-3, the degradation of poly-(ADP-ribose) polymerase (PARP) and D4-GDI, and DNA fragmentation, which were blocked by pre-treatment with acetyl-Asp-Glu-Val-Asp- dialdehyde (Ac-DEVD-CHO). Treatment that combined 25 M DADS and 100 nM daunorubicin caused a similar degree of caspase-3 activation, PARP and D4-GDI degradation, and DNA fragmentation to that caused by treatment with 250 nM daunorubicin alone. These results indicate that combined therapy using daunorubicin with DADS, a component of food, and garlic can effectively decrease the therapeutic dose of daunorubicin, preventing the severe side effects of daunorubicin.

• Journal of Microbiology and Biotechnology
• /
• v.19 no.9
• /
• pp.946-950
• /
• 2009

In the course of screening for apoptotic substances that induce apoptosis in human leukemia U937 cells, a fungal strain, F000487, which exhibits potent inducible activity, was selected. The active compound was purified from an ethyl acetate extract of the microorganism by Sep-pak $C_{18}$ column chromatography and HPLC, and was identified as atromentin by spectroscopic methods. This compound induced caspase-3 processing in human leukemia U937 cells. The caspase-3 and poly (ADP-ribose) polymerase (PARP) were induced by atromentin in a dose-dependent manner. Furthermore, DNA fragmentation was also induced by this compound in a dose-dependent manner. These results show that atromentin potently induces apoptosis in U937 cells and that atromentin-induced apoptosis is related to the selective activation of caspases.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.313.3-314
• /
• 2002

Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in response to a variety of cytokines and other proinflammatory stimuli. It has been known that aberrant up-regulation of COX-2 is associated with resistance to apoptosis. Contrary to the above notion. treatment of MCF10A-ras cells with the anti-tumor agent ET -18-O-$CH_3$ caused increased expression of COX-2 and its mRNA transcript. while inducing apoptosis as revealed by proteolytic cleavage of poly(ADP-ribose)polymerase. caspase-3 activation, and positive TUNEL staining. (omitted)

• Toxicological Research
• /
• v.18 no.3
• /
• pp.259-265
• /
• 2002

Resveratrol, a phytoalexin found in grapes, berries, and peanuts, is one of the most promising agents for cancer prevention. Recent studies show that the antitumor activity of resveratrol occurs through p53-mediated apoptosis. This study demonstrated the mechanism that resveratrol induced apoptosis in human osteosarcoma Saos-2 cells lacking p53. Treatment of osteosarcoma Saos-2 cells with resveratrol resulted in decrease of cell viability, which was revealed as apoptosis characterized by activation of caspase-3 protease as well as cleavage of poly(ADP-ribose) polymerase (PARP) with change of mitochondrial membrane potential transition. These results suggest that resveratrol may be potentially useful to treat osteosarcoma via activation of caspase protease and mitochondrial dysfunction.