• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6409-6413
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• 2012

The innate immune system coordinates the inflammatory response to pathogens. To do so, its cells must discriminate self from non-self utilizing receptors that identify molecules synthesized exclusively by microbes. Toll-like receptors have a crucial role in the detection of microbial infection in mammals and insects. In mammals, they have evolved to recognize conserved products unique to microbial metabolism. These include lipopolysaccharide (LPS), lipotechoic acids, and peptidoglycans (PGN). We show here that TLRs, including TLR2, are expressed on the THP-1 human leukemia cell line. Activation of TLR2 signaling in THP-1 by PGN induces the synthesis of various soluble factors and proteins including interleukin-$1{\beta}$, interleukin-8 and TNF-${\alpha}$ and apoptosis of THP-1 with PGN dose and time dependence. Moreover, in this study we show that PGN induces apoptosis of THP-1 cells in a TNF-${\alpha}$-dependent manner. These findings indicate that TLR2 signaling results in a cascade leading to tumor apoptosis and differentiation, which may suggest new clinical prospects using TLR2 agonists as cytotoxic agents in certain cancers.

• 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.

• 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.

• The Journal of Internal Korean Medicine
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• v.32 no.4
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• pp.565-583
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• 2011

Objectives : This study investigated the biochemical mechanisms of anti-proliferative and pro-apoptotic effects of the water extract of Dan-Seon-Tang (DST) in human leukemia U937 cells. Methods : U937 cells were exposed to DST and growth inhibition was measured by MTT assay. Results : Exposure of U937 cells to DST resulted in the growth inhibition in a concentration-dependent manner. This inhibitory effect was associated with morphological changes and apoptotic cell death such as formation of apoptotic bodies, increased populations of apoptotic-sub G1 phase and induction of DNA fragmentation. The induction of apoptotic cell death in U937 cells by DST was associated with up-regulation of death receptor 4 (DR4) and down-regulation of Bid, surviving and cellular inhibition of apoptosis protein-2 (cIAP-2) expression. DST treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant degradation of caspase-3 substrate proteins such as poly (ADP-ribose) polymerase (PARP), phospholipase (PLC)-${\gamma}1$, ${\beta}$-catenin and DNA fragmentation factor 45/inhibotor of caspase activated DNAse (DFF45/ICAD). Furthermore, apoptotic cell death by DST was significantly inhibited by caspase-3 specific inhibitor z-DEVD-fmk, demonstrating the important role of caspase-3. Conclusions : These findings suggest that herb prescription DST may be a potential chemotherapeutic agent for the control of human leukemia U937 cells; further study is needed to identify the active compounds.

• Journal of Microbiology and Biotechnology
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• v.22 no.2
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• pp.264-269
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• 2012

Recently, we reported that the synthetic Coprisin analog peptide 9-mer dimer CopA3 (consisted of all-L amino acid sequence) was designed based on a defensin-like peptide, Coprisin isolated from Copris tripartitus. The 9-mer dimer CopA3 (L-CopA3) had antibacterial activity and induced apoptosis in human leukemia cells via a caspase-independent pathway. In this study, all of amino acid sequences of L-CopA3 were modified to all D-form amino acids (DCopA3) to develop a more effective antimicrobial peptide. We investigated whether D-CopA3 had antimicrobial activities against pathogenic microorganisms and pro-apoptotic effects in human leukemia cells (U937, Jurkat, and AML-2). The synthetic peptide D-CopA3 had antimicrobial activities against various pathogenic bacteria and yeast fungus with MIC values in the 4~64 ${\mu}M$ range. Moreover, D-CopA3 caused cell growth inhibition, and increased the chromosomal DNA fragmentation and the expression of inflammatory cytokines, TNF-${\alpha}$ and IL1-${\beta}$, transcripts in human leukemia cells. The all-D amino acid peptide DCopA3 proved as effective as the L-CopA3 reported previously. These results provide the basis for developing D-CopA3 as a new antibiotic peptide.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5339-5343
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• 2012

The induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies. Bufalin is a cardiotonic steroid that has the potential to induce differentiation and apoptosis of tumor cells. Research on bufalin has so far mainly involved leukemia, prostate cancer, gastric cancer and liver cancer, and has been confined to in vitro studies. The bufadienolides bufalin and cinobufagin have been shown to induce apoptosis in a wide spectrum of cancer cell. The present article reviews the anticancer effects of bufalin. It induces apoptosis of lung cancer cells via the PI3K/Akt pathway and also suppressed the proliferation of human non-small cell lung cancer A549 cell line in a time and dose dependent manner. Bufalin, bufotalin and gamabufotalin, key bufadienolides, significantly sensitize human breast cancer cells with differing ER-alpha status to apoptosis induction by the TNF-related apoptosis-inducing ligand (TRAIL). In addition, bufadienolides induce prostate cancer cell apoptosis more significantly than that in breast epithelial cell lines. Similar effects have been observed with hepatocellular carcinoma (HCC) but the detailed molecular mechanisms of inducing apoptosis in this case are still unclear. Bufalin exerts profound effects on leukemia therapy in vitro. Results of multiple studies indicate that bufalin has marked anti-tumor activities through its ability to induce apoptosis. Large-scale randomized, double-blind, placebo or positive drug parallel controlled studies are now required to confirm the efficacy and apoptosis-inducing potential of bufalin in various cancers in the cliniucal setting.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.9
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• pp.1201-1207
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• 2011

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed as a potent tool to trigger apoptosis in cancer therapy. However, as many types of cancer cells remain resistant towards TRAIL-induced cytotoxicity, several combined therapy approaches aimed to sensitize cells to TRAIL have been developed. Genistein, a natural isoflavonoid phytoestrogen, has been shown to have anticancer activity by inducing cell cycle arrest at G2M phase as well as apoptosis in various cancer cell lines. In the present study, we showed that treatment with TRAIL in combination with subtoxic concentrations of genistein sensitized U937 human leukemia cells to TRAIL-mediated apoptosis. Combined treatment with genistein and TRAIL effectively activated caspases through Bid truncation (tBid) and down-regulation of cellular caspase-8 (FLICE)-like inhibitory proteinL ($cFLIP_L$). However, the apoptotic effects of co-treatment with genistein and TRAIL were significantly inhibited by specific caspase inhibitors, which demonstrates the important role of caspases in apoptosis induced by genistein and TRAIL. Overall, our results indicate that genistein can potentiate TRAIL-induced apoptosis through down-regulation of $cFLIP_L$ and up-regulation of pro-apoptotic tBid proteins.

• 대한동의생리학회:학술대회논문집
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• 2005.07a
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• pp.13-13
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• 2005

• Proceedings of the Korean Society of Life Science Conference
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• 2008.10a
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• pp.88.1-88.1
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• 2008

• Proceedings of the Korean Society of Life Science Conference
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• 2008.10a
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• pp.88.2-88.2
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• 2008