• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.12
• /
• pp.7537-7542
• /
• 2013

Background: Terpinen-4-ol, a monoterpene, is found as the main component of essential oil extracts from many plants. In this study apoptotic and autophagic types of cell death induced by terpinen-4-ol and associated mechanisms were investigated in human leukemic HL-60 cells. Materials and Methods: The cytotoxicity of human leukemic U937 and HL-60 cells was determined by MTT assay. Cytochrome c release, expression of Bax, Bcl-2, Bcl-xl and cleaved Bid were determined by Western blotting. Cell morphology was examined under a transmission electron microscope. LC3-I/II, ATG5 and Beclin-1 levels were detected by immunoblotting. Results: Terpinen-4-ol exhibited cytotoxicity to human leukemic HL-60 but not U937 cells. The apoptotic response to terpinen-4-ol in HL-60 cells was due to induction of cytochrome c release from mitochondria and cleavage of Bid protein after the stimulation of caspase-8. There was a slightly decrease of Bcl-xl protein level. The characteristic cell morphology of autophagic cell death was demonstrated with multiple autophagosomes in the cytoplasm. At the molecular level, the results from Western blot analysis showed that terpinen-4-ol significantly induced accumulation of LC3-I/II, ATG5 and Beclin-1, regulatory proteins required for autophagy in mammalian cells. Conclusions: Terpinen-4-ol induced-human leukemic HL-60 cell death was via both autophagy and apoptosis.

• Preventive Nutrition and Food Science
• /
• v.11 no.1
• /
• pp.17-24
• /
• 2006

Methanolic and aqueous extracts from 37 seaweed species (10 green and 27 brown seaweeds) collected from Jeju Island coast were prepared at high ($70^{\circ}C$) and room ($20^{\circ}C$) temperatures and examined for cytotoxic activity against 4 tumor cell lines: U937 (human monoblastoid leukemia cell line), HL60 (human promyelocytic leukemia cell line), HeLa (woman cervical carcinoma cell line) and CT26 (mouse colon carcinoma line). Both MeOH extracts of Desmarestia tabacoides and Dictyota dichotoma possessed strong cytotoxic activities against all the tumor cell lines tested, but the aqueous extract exhibited no activity. On the other hand Ecklonia cava showed strong cytotoxic activities for the $20^{\circ}C$ aqueous extract against the three tumor cells except HeLa cell. Sagassum coreanum and Sagassum siliquastrum $20^{\circ}C$ aqueous extracts also exhibited strong cytotoxic activities against U937, HL60, HeLa cells. Even though green seaweeds showed less activity than brown seaweeds, $20^{\circ}C$ aqueous extracts of Codium contractum and Codium fragile exhibited strong cytotoxic activities against HL60 or CT26 cells, respectively.

• Preventive Nutrition and Food Science
• /
• v.11 no.3
• /
• pp.177-183
• /
• 2006

Methanolic and aqueous extracts of 26 red algae species collected from Jeju Island coast were prepared at a high $(70^{\circ}C)$ and a room temperature $(20^{\circ}C)$ and were examined for their cytotoxic activity against 4 tumor cell lines: U-937 (human monoblastoid leukemia cell line), HL-60 (human promyelocytic leukemia cell line), B-16 (murine melanoma cell line) and HeLa (woman cervical carcinoma cell line). $20^{\circ}C$ methanolic extract of Polysiphonia japonica showed cytotoxic activity of over 50% against U-937, HL-60 and B-16 cells. On the other hand, the $20^{\circ}C$ aqueous extract of Scinaia okamurae and $70^{\circ}C$ aqueous extract of Chondrus crispus showed cell growth inhibition activity of more than 50% against HL-60 and B-16 cells. The highest cytotoxic activity was observed in the $20^{\circ}C$ aqueous extract of Scinaia okamurae against B-16 cells (80.55%).

• Food Science and Biotechnology
• /
• v.15 no.3
• /
• pp.369-373
• /
• 2006

Water extracts obtained from cultured mountain ginseng (CMG) were evaluated for their ability to stimulate immune cells and inhibit cancer cell proliferation. The lymphocyte subpopulation in mouse splenocytes in vivo was significantly increased by the administration of the CMG extract (27.4 mg/mouse). Interleukin-2 and ${\gamma}$-interferon in the mice serum increased up to 30% in CMG extract-treated mice. At a concentration of 1.37 mg/mL, nitric oxide increased up to 400% in the macrophage cell line treated with CMG extract. The CMG extract significantly retarded the proliferation of human acute promyelocytic (HL60), human histiocytic (U937), and mouse lymphocytic (L1210) leukemia cell lines in vitro at concentrations over 2.74-13.7 mg/mL. In addition, CMG extract treatments (1.37 mg/mL and 2.74 mg/mL) lead to the increased expression of the p53 gene and protein in cultured U937 leukemia cell lines. These results indicate that water extracts of CMG are capable of both immune cell stimulation and cancer cell growth inhibition.

• Archives of Pharmacal Research
• /
• v.17 no.3
• /
• pp.135-138
• /
• 1994

Acyclonucleoside homologues of 1-$(\omega$-cyabnoalkyl)-and 1, 3-bis $(\omega$-cyanoalkyl) uracils were synthesized by the series of alkylation reactions of uracil with the $\omega$-chloroalkyl nitrile ${(Cl-(CH}_2)_n$-CN;n=1, 2, 3, 4) in DMSO under $50-70^circ{C}$ temperature. The 1-$(\omega$-cyanoalkyl)-and 1, 3-bis$(\omega$-cyanoalkyl) uracils were separated either by the fractional crystallization or column chromatography. The antitumor activities for these synthesized compounds were determined against four cell lines (J-82 cell, P388 cell, FM-3A cell and U-937 cell lines). These compounds failed to exhibit any significant antitumor activity.

• Preventive Nutrition and Food Science
• /
• v.9 no.3
• /
• pp.265-269
• /
• 2004

Prunus mandshurica var. glabra Nakai (Rosaceae) is widely distributed in South Korea and bears a fruit with a bitter and astringent taste. An ethyl acetate-soluble extract of Prunus mandshurica was found to exhibit significant cytotoxicity against human leukemia cell lines. Bioassay-directed fractionation of this extract using an MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) cell proliferation assay as a monitor led to the isolation of the bioactive compounds. Two compounds, 1 and 2 were subsequently found to mediate cytotoxicity against U937, human monocytic leukemia cells. The 50% growth inhibitory concentrations ($IC_{50}$/) of compounds 1 and 2 on U937 were 40 and 62 $\mu\textrm{g}$/mL, respectively.

• Journal of Life Science
• /
• v.25 no.1
• /
• pp.53-61
• /
• 2015

In this study, we tried to separate the photosensitizer that induces apoptosis of leukemia cells (U937) from perilla leaves. Perilla leaves (Perilla frutescens Britt var. japonica Hara) are a popular vegetable in Korea, being rich in vitamins (A and E), GABA, and minerals. Dried perilla leaves were extracted with methanol to separate the photosensitizer by various chromatographic techniques. The structure of the isolated compound (PL9443) was identified by 1D-NMR, 2D-NMR, and FAB-mass spectroscopy. Absorbance of the UV-Vis spectrum was highest at 410 nm and was confirmed by the 330, 410, and 668 nm. PL9443 compound was determined to be pheophorbide, an ethyl ester having a molecular weight of 620. It was identified as a derivative compound of pheophorbide structure when magnesium comes away from a porphyrin ring. Observation of morphological changes in U937 cells following cell death induced by treated PL9443 compound revealed representative phenomena of apoptosis only in light irradiation conditions (apoptotic body, vesicle formation). Results from examining the cytotoxicity of PL9443 substance against U937 cells showed that inhibition rates of the cell growth were 99.9% with the concentration of 0.32 nM PL9443. Also, the caspase-3/7 activity was 99% against U937 cells with the concentration of 0.08 nM of PL9443 substance. The result of the electrophoresis was that a DNA ladder was formed by the PL9443. The PL9443 compound is a promising lead compound as a photosensitizer for photodynamic therapy of cancer.

• The Journal of Korean Society of Virology
• /
• v.29 no.2
• /
• pp.129-136
• /
• 1999

Transient transfection assay has been done to evaluate whether the c-jun activation would be prerequisite to the induction of permissiveness against human cytomegalovirus using in vitro cell model in which U937 has been induced to express CD11b and CD14 to become potential monocyte/macrophage cells by TPA treatment. U937 cells were treated with $10\;{\mu}M$, $50\;{\mu}M$ or $100\;{\mu}M$ of TPA. The cell morphology change was observed and the expression of the CD11b and CD14 was confirmed by FACS. Differentiated cells were transfected with pJLuc reporter vector which contained the wild type murine c-jun promoter spanning the SP1, CTF, ATF/CREB and MEF-2 binding sites upstream of the firefly luciferase gene. After 48 hrs of transfection, the cells were infected with HCMV Towne strain and the luciferase activity was assessed at 1 hand 4 h pi. The transfection assay showed no activation of the c-jun promoter at 1 h pi, instead, it showed 2 times increase of the its activity at 4 h pi. There was no difference of the c-jun promoter activation between TPA treated and untreated U937 cells, implying that c-jun activation might not be prerequisite for allowing cells to be premissive to HCMV, although HCMV infection itself could activate c-jun promoter.

• Journal of Life Science
• /
• v.23 no.8
• /
• pp.1057-1063
• /
• 2013

Citri Pericarpium is one of the most commonly used traditional herbal medicines in Korea, China, and Japan. Its extracts have many properties including the treatment of indigestion and inflammatory respiratory syndromes such as bronchitis and asthma. However, the underlying molecular mechanisms of anti-cancer activity and molecular targets are not fully understood. In this work, we investigated the anti-proliferative activity of Citri Pericapium (EMCP) methanol extract on reactive oxygen species (ROS) production and the association of these effects with apoptotic cell death using U937 human leukemia cells in vitro. EMCP treatment decreased cell proliferation in a dose-dependent manner following an increase of the sub-G1 phase, the down-regulation of Bax proteins, the activation of caspases, the degradation of poly (ADP-ribose) polymerase proteins (PARP), and the induction of ROS generation. However, the quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the EMCP-induced apoptosis effects. In addition, heme oxygenase-1 expression also recovered by inhibiting the nuclear translocation of phosphorylated NF-E2-related factor 2. Taken together, our data indicate that ROS are involved as key mediators in the early molecular events in the EMCP-induced apoptotic pathway.

• Journal of Life Science
• /
• v.25 no.2
• /
• pp.249-255
• /
• 2015

Schisandrae fructus [Schizandra chinensis (Turcz.) Baillon] is a medicinal herb widely used for treating various inflammatory and immune diseases in East Asian countries. The Schisandrae Semen essential oil (SSeo) from this plant has pharmacological activities, including antioxidant, antimicrobial, and antitumoral activities. Nevertheless, the biological activities and underlying molecular mechanisms of the potential anti-cancer effects of this oil remain unclear. In the present study, we investigated the potential inhibition of apoptosis signaling pathways by SSeo in human leukemia U937 cells and evaluated the underlying molecular mechanism. Exposure to SSeo resulted in a concentration-dependent growth inhibition due to apoptosis, which was verified by DNA fragmentation, the presence of apoptotic bodies, and an increase in the sub-G1 ratio. Induction of apoptotic cell death by SSeo was correlated with the down-regulation of members of the inhibitor of apoptosis protein (IAP) family (including X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and surviving) and anti-apoptotic Bcl-2, and with up-regulation of death receptor (DR) 4 and DR5, depending on dosage. SSeo treatment also induced Bid truncation, mitochondrial dysfunction, proteolytic activation of caspase-3, -8 and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase. Taken together, these findings suggest that SSeo may be a potential chemotherapeutic agent for use in the control of human leukemia cells. Further studies are needed to identify its active compounds.