• Archives of Pharmacal Research
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• v.20 no.1
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• pp.29-33
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• 1997

The effects of ursodeoxycholic acid (UDCA) and its novel derivative, named as HS-1030, on the proliferation of HepG2, human hepatocellular carcinoma cells were investigated. Whereas UDCA had no significant effect in a concentration range we have tested, HS-1030 inhibited the proliferation of HepG2 cells in a concentration dependent manner. Surprisingly, HS-1030 had no effect on the proliferation of Human Chang liver cell which is a normal liver cell line. We also found that proliferation-inhibitory effect of HS-1030 was due to the induction of apoptosis of HepG2 cells, which was confirmed by observing the internucleosomal DNA fragmentation and morphological changes (ie., cell shrinkage, nuclear condensation and the formation of apoptotic bodies). These results suggest that HS-1030 may be a good candidate as a drug for the treatment of liver cancer.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.13 no.1
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• pp.17-27
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• 1983

The author observed the effects of /sup 60/Co irradiation on the development and subcellular structure of tongue tissue of the fetal rats. The lower left abdomen of mothers were exposed to radiation on 15½th day of gestation with 300R. The fetuses were removed on the 6hr, 14hr, 24hr, 48hr and 72hr after irradiation and the light microscopic and electron microscopic observations of the lingual epithelium, lamina propria and muscle layer were carried out. The results were as follows: 1. The irradiated fetuses showed the retardation of filiform papillae formation. 2. Epithelial cells revealed fusion and myelination of mitochondria, large autolysosomes, increased lipid droplets, retardation of tonofilaments and desmosome formation. 3. In the lamina propria, undifferentiated cells showed bleb formation of nuclear membrane, pyknosis and fragmentation of nucleus, edema of cytoplasm I and nucleus, increased auto-lysosomes, dilatation of cell membrane and cell necrosis. Also, collagenous fibril formation was inhibited by irradiation. 4. In the muscle layer, growth of myotubes was inhibited. Myotubes showed swelling of mitochondria, loss of mitochondrial cristae, autolysosomes, retardation of myofibril formation, and large vacuoles. Undifferentiated cells adjacent myotube contained pyknotic nucleus and autolysosomes. 5. Among the various tissues of tongue, it seems that mesenchymal cells were most radiosensitive.

• International Journal of Oral Biology
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• v.41 no.4
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• pp.175-181
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• 2016

Tyrosol, a phenylethanoid and a derivative of phenethyl alcohol, possesses various biological properties, such as anti-oxidative and cardioprotective activity. Olive oil is the principal source of tyrosol in the human diet. However, so far the anti-cancer activity of tyrosol has not yet been well defined. This study therefore undertakes to examine the cytotoxic activity and the mechanism of cell death exhibited by tyrosol in KB human oral cancer cells. Treatment of KB cells with tyrosol induced the cell growth inhibition in a concentration- and a time-dependent manner. Furthermore, the treatment of tyrosol induced nuclear condensation and fragmentation of KB cells. Tyrosol also promoted proteolytic cleavage of procaspase-3, -7, -8 and -9, increasing the amounts of cleaved caspase-3, -7, -8 and -9. In addition, tyrosol increased the levels of cleaved PARP in KB cells. These results suggest that tyrosol induces the suppression of cell growth and cell apoptosis in KB human oral cancer cells, and is therefore a potential candidate for anti-cancer drug discovery.

• YAKHAK HOEJI
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• v.56 no.3
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• pp.173-179
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• 2012

Saussurea lappa (SL) and major compounds, sesquiterpene lactones, have been suggested to possess various biological effects, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral and cardiotonic activities. Therefore, the ethanol extract of Saussurea lappa root (ESL) is studied for the mechanism of its action in apoptotic pathway. ESL-treated cells manifested nuclear condensation, and fragmentation. ESL also triggered the mitochondrial apoptotic pathway, as indicated by a change in Bax/Bcl2 ratio and caspase-9/-3 activation. ESL induced p38 MAPK/JNK, p53, and ASK1 phosphorylation. ROS scavenger reversed ESL-induced apoptotic cell death via inhibition of caspase-3 and p38 MAPK/JNK phosphorylation. These results suggest that ESL induced apoptosis in HepG2 cells through the ROS-p38/JNK pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3395-3403
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• 2016

Conjugated linoleic acid, a functional lipid, produced from Lactobacillus plantarum (LP-CLA), has been demonstrated to possess apoptotic activity. The anti-proliferative and apoptotic potential of LP-CLA was here evaluated in vitro using the MDA-MB-231 human breast cancer cell line as a model system. Proliferation of MDA-MB-231 cells was inhibited with increasing concentrations of LP-CLA with altered morphological features like cell detachment, rounding of cells and oligonucleosomal fragmentation of DNA. Flow cytometry confirmed the apoptotic potential of LP-CLA by ANNEXIN V/PI double staining. Furthermore, outcome results indicated that the apoptosis was mediated by downregulation of the NF-${\kappa}B$ pathway which in turn acted through proteasome degradation of $I{\kappa}B{\alpha}$, inhibition of p65 nuclear translocation, release of cytochrome-C from mitochondria and finally overexpression of Bax protein. Thus, conjugated linoleic acid, a natural product derived from probiotics, could therefore be a possible potential chemotherapeutic agent due to its apoptotic activity against estrogen receptor negative breast cancer cells.

• Molecules and Cells
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• v.23 no.2
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• pp.170-174
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• 2007

High-throughput subcellular imaging is a powerful tool for investigating the function of genes. In order to identify novel regulators of apoptosis we transiently transfected HeLa cells with 938 hypothetical genes of unknown function, and captured their nuclear images with an automated fluorescence microscope. We selected genes that induced greater than 3-fold increase in the percentage of apoptotic nuclei compared with vector-transfected cells. The full-length genes C10orf61, MGC 26717, and FLJ13855 were identified as candidate proapoptotic genes, and their apoptotic effects were confirmed by DNA fragmentation ELISAs and Western blotting for caspase-7 and PARP. We conclude that a subcellular image-based apoptotic screen is useful for identifying genes with proapoptotic activity.

• Archives of Pharmacal Research
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• v.26 no.2
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• pp.157-161
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• 2003

The major ingredient of Persicae Semen is a cynogenic compound, amygdalin (D-mandelonitrile-$\beta$-gentiobioside). Controversial results on the anticancer activity of amygdalin were reported due to its conversion to its inactive isomer, neoamygdalin. In order to inhibit the epimerization of amygdalin, we used newly developed simple acid boiling method in preparation of Persicae Semen extract. HPLC analysis revealed most of amygdalin in Persicae Semen extract was active D-form. Persicae Semen extract was used to analyze its effect on cell proliferation and induction of apoptosis in human promyelocytic leukemia (HL-60) cells. Persicae Semen extract was cytotoxic to HL-60 cells with $IC_{50}$ of 6.4 mg/mL in the presence of 250 nM of $\beta$-glucosidase. The antiproliferative effects of Persicae Semen extract appear to be attributable to its induction of apoptotic cell death, as Persicae Semen extract induced nuclear morphology changes and internucleosomal DNA fragmentation.

• Journal of Microbiology and Biotechnology
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• v.25 no.4
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• pp.439-447
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• 2015

The objective of this study was to isolate and identify the chemical structure of a biosurfactant produced by Nocardia farcinica strain BN26 isolated from soil, and evaluate its in vitro antitumor activity on a panel of human cancer cell lines. Strain BN26 was found to produce glycolipid biosurfactant on n-hexadecane as the sole carbon source. The biosurfactant was purified using medium-pressure liquid chromatography and characterized as trehalose lipid tetraester (THL) by nuclear magnetic resonance spectroscopy and mass spectrometry. Subsequently, the cytotoxic effects of THL on cancer cell lines BV-173, KE-37 (SKW-3), HL-60, HL-60/DOX, and JMSU-1 were evaluated by MTT assay. It was shown that THL exerted concentration-dependent antiproliferative activity against the human tumor cell lines and mediated cell death by the induction of partial oligonucleosomal DNA fragmentation. These findings suggest that THL could be of potential to apply in biomedicine as a therapeutic agent.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.374-380
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• 2000

Propentofylline (PPF, 3-methyl-1-(5-oxohexyl)-7-propylxanthine) has been reported to be a compound for treatment of both vascular dementia and dementia of the Alzheimer type. The short half-life (about 15 min) of PPF at the terminal elimination phase and poor bioavailability after oral administration of PPF to rabbits (Kim et al., 1992) suggest in part that this drug takes the extensive first-pass metabolism in the liver. In addition, the metabolic pathway for PPF remains unclear. The objective of this experiment is to identify urinary metabolites of PPF in rats. For the identification of the metabolites, rat urine was collected after oral administration of 100${m}g/kg$ PPF. PPF metabolite, 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine, was synthesized and confirmed by gas chromatography/mass spectroscopy (GC/MS) and $^1H$ nuclear magnetic resonance spectroscopy. The urinary metabolites of PPF were extracted with diethyl ether and identified by electron impact and chemical ionization GC/MS. One urinary metabolite was confirmed to be 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine by synthesized authentic compound. Several metabolites of monohydroxy- and dihydroxy-PPF were identified based on mass fragmentation of both intact and trimethylsilylated derivatives of PPF metabolites and the novel structure of these metabolites is suggested based on mass spectra.

• BMB Reports
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• v.37 no.4
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• pp.445-453
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• 2004

We identified apoptosis as being a significant mechanism of toxicity following the exposure of HeLa cell cultures to abrin holotoxin, which is in addition to its inhibition of protein biosynthesis by N-glycosidase activity. The treatment of HeLa cell cultures with abrin resulted in apoptotic cell death, as characterized by morphological and biochemical changes, i.e., cell shrinkage, internucleosomal DNA fragmentation, the occurrence of hypodiploid DNA, chromatin condensation, nuclear breakdown, DNA single strand breaks by TUNEL assay, and phosphatidylserine (PS) externalization. This apoptotic cell death was accompanied by caspase-9 and caspase-3 activation, as indicated by the cleavage of caspase substrates, which was preceded by mitochondrial cytochrome c release. The broad-spectrum caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD-fmk), prevented abrin-triggered caspase activation and partially abolished apoptotic cell death, but did not affect mitochondrial cytochrome c release. These results suggest that the release of mitochondrial cytochrome c, and the sequential caspase-9 and caspase-3 activations are important events in the signal transduction pathway of abrin-induced apoptotic cell death in the HeLa cell line.