• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.2
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• pp.452-458
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• 2005

Cordyceps militaris is a medicinal fungus, which has been used for patient suffering from cancer in Oriental medicine. It was reported previously that C. militaris extracts are capable of inhibiting tumor growth, however, the anti-poliferative effects of human cancer cells have not been poorly understood. In this study, to elucidate the growth inhibitory mechanisms of human cancer cells by treatment of aqueous extract of C. militaris (AECM) we investigated the anti-proliferative effects of AECM in human leukemia U937 cell line. AECM treatment inhibited the growth of U937 cells and induced the apoptotic cell death in a concentration-dependent manner, which was associated with morphological changes. We observed the up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1) by p53-independent manner and activation of caspase-3 in AECM-treated U937 cells, however, the activity of caspase-9 was remained unchanged. Additionally, AECM treatment caused a dose-dependent inhibition of the expression of telomere regulatory gene products such as human telomere reverse transcriptase (hTERT) and telomerase-associated protein-1 (TEP-1). Taken together, these findings suggest that AECM-induced inhibition of human leukemic cell proliferation is associated with the induction of apoptotic cell death via modulation of several major growth regulatory gene products, and C. militaris may have therapeutic potential in human lung cancer.

• Biomolecules & Therapeutics
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• v.15 no.3
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• pp.145-149
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• 2007

We have previously shown that 2,4,3',5'-tetramethoxystilbene (TMS), a synthetic trans-stilbene analogue acting as a potent inhibitor of human cytochrome P450 1B1, induces apoptotic cell death in human cancer cells. In the present studies, we report the mechanisms of apoptotic cell death by TMS in human promyelocytic leukemic HL-60 cells. We found that treatment of HL-60 cells with TMS suppressed the cell growth in a concentration-dependent manner with $IC_{50}$ value of about 0.8 ${\mu}M$. Immunoblot experiments revealed that DMHS-induced apoptosis was associated with cleavage of poly (ADP-ribose) polymerase. The release of cytochrome c from mitochondria into the cytosol was significantly increased in response to TMS. TMS caused activation of caspase-3 in a concentration-dependent manner and TMS-mediated caspase-3 activation was partially prevented by the caspase inhibitor, zVAD-fmk. Interestingly, we found that the cytotoxic effect of anticancer drugs such as paclitaxel, docetaxel, or etoposide was enhanced in the presence of TMS. Simultaneous treatment with TCDD also significantly increased cytotoxic effects of TMS alone or TMS and anti-cancer agents. Taken together, our present results indicated that TMS leads to apoptotic cell death in HL-60 cells through activation of caspase-3 activity and release of cytochrome c into cytosol. The ability of TMS to increase cytotoxic effect of anticancer drugs may contribute to its usefulness for cancer chemotherapy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.6
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• pp.1636-1639
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• 2005

To develop novel anti-leukemic medicine, we have prepared a Korean traditional medicine, named Hang-baek-Tang, which is composed of 8 kinds of anti-leukemic medicinal plants. The water extracts was examined anti-leukemic activity using the human leukemia cell line, HL-60 cells. HL-60 cells showed the growth inhibition and several apoptotic features, including DNA ladders, morphological changes, by treatment of the cells with Hang-Daek-Tang. We have observed that Hang-baek-Tang induced the activation of caspase-3, caspase-8 and caspase-9. Further molecular analysis demonstrated that Hang-baek-Tang induced cleavage of PARP and increase of hypodiploid (Sub-G1) population in flow cytometric analysis. These results indicate that Hang-baek-Tang has been considered to exert anti-leukemic activity through the procaspase-3 activation pathway.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.205.1-205.1
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• 2001

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.170.2-170.2
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• 2001

• Nutrition Research and Practice
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• v.8 no.2
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• pp.132-137
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• 2014

BACKGROUND/OBJECTIVES: In this study, the apoptogenic activity and mechanisms of cell death induced by hexane extract of aged black garlic (HEABG) were investigated in human leukemic U937 cells. MATERIALS/METHODS: Cytotoxicity was evaluated by MTT (3-(4, 5-dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazoliumbromide) assay. Apoptosis was detected using 4,6-diamidino-2-phenyllindile (DAPI) staining, agarose gel electrophoresis and flow cytometry. The protein levels were determined by Western blot analysis. Caspase activity was measured using a colorimetric assay. RESULTS: Exposure to HEABG was found to result in a concentration- and time-dependent growth inhibition by induction of apoptosis, which was associated with an up-regulation of death receptor 4 and Fas legend, and an increase in the ratio of Bax/Bcl-2 protein expression. Apoptosis-inducing concentrations of HEABG induced the activation of caspase-9, an initiator caspase of the mitochodrial mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase. HEABG also induced apoptosis via a death receptor mediated extrinsic pathway by caspase-8 activation, resulting in the truncation of Bid, and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. However, pre-treatment of U937 cells with the caspase-3 inhibitor, z-DEVD-fmk, significantly blocked the HEABG-induced apoptosis of these cells, and increased the survival rate of HEABG-treated cells, confirming that HEABG-induced apoptosis is mediated through activation of caspase cascade. CONCLUSIONS: Based on the overall results, we suggest that HEABG reduces leukemic cell growth by inducing caspase-dependent apoptosis through both intrinsic and extrinsic pathways, implying its potential therapeutic value in the treatment of leukemia.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.465-469
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• 2015

Background: Orostachys japonicus A. Berger (A. Berger) is commonly used as a folk remedy for cancer therapy. However, the mechanisms of its anti-cancer activity are poorly investigated in human cancer cells. In this study, we investigated whether flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) might have anticancer effects in human leukemia cells, focusing on cell death mechanisms. Materials and Methods: U937 human leukemic cancer cells were used. Results: FEOJ induced apoptosis in a dose-dependent manner in human U937 cancer cells. Flow cytometry revealed significant accumulation of cells with sub-G1 DNA content at the concentrations of $200{\mu}g/mL$ and $400{\mu}g/mL$. FEOJ-induced apoptosis was caspase-dependent through loss of mitochondrial membrane potential (MMP, ${\Delta}{\Psi}m$) in human U937 cancer cells, which might be associated with suppression of Bcl-2 and XIAP proteins. FEOJ induced the p38 MAPK signaling pathway, playing at least in part an important role in FEOJ-induced apoptosis. Conclusions: This study suggested that FEOJ may induce caspase-dependent apoptosis in human leukemic cells by regulating MMP (${\Delta}{\Psi}m$) through suppressing Bcl-2 and X-IAP. In addition, the results indicated that upstream p38 MAPK signaling regulates the apoptotic effect of FEOJ. This study provides evidence that FEOJ might have anti-cancer potential for human leukemic cells.

• Journal of Life Science
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• v.16 no.4
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• pp.589-597
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• 2006

Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinase and DNA topoisomerase activities. There are several studies documenting molecular alterations leading to cell cycle arrest and induction of apoptosis by genistein as a chemopreventive agent in a variety of cancer cell lines; however, its mechanism of action and its molecular targets on human bladder carcinoma and leukemic cells remain unclear. In the present study, we have addressed the mechanism of action by which genistein suppressed the proliferation of T24 bladder carcinoma and U937 leukemic cells. Genistein significantly inhibited the cell growth and induced morphological changes, and induced the G2/M arrest of the cell cycle in both T24 and U937 cells with a relatively stronger cytotoxicity in U937. The G2/M arrest in T24 cells was associated with the inhibition of cyclin A, cyclin B1 and Cdc25C protein expression without alteration of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1). However, the inhibitory effects of genistein on the cell growth of U937 cells were connected with a marked inhibition of cyclin B1 and an induction of Cdk inhibitor p21 proteins by p53-independent manner. These data suggest that genistein may exert a strong anticancer effect and additional studies will be needed to evaluate the different mechanisms between T24 and U937 cells.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.421-427
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• 2002

For probing the importance of planarity of imidazolidinone motif of 4-phenyl-1-(N-acylindoline-5-sulfonyl)imidazolidinones 1 for their cytotoxicity, 4-phenyl-1-(N-acylindoline-5-sulfonyl)[1,2,5]thiadiazolidine-1,1-dioxides 2 were prepared and their cytotoxicity were measured against human lung carcinoma (A549), human colon carcinoma (COLO205), human ovarian cancer (SK-OV-3), human leukemic cancer (K562), and murine colon adenocarcinoma (Colon26) cell lines in vitro. Although only carbonyl moiety of imidazolidinone ring was replaced with sulfonyl group, compounds 2 do not show any activity against all five cancer cell lines unlike 1. Therefore the planarity of imidazolidinone ring of 1 should be an important factor for their cytotoxic activity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.629-632
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• 2003

Scutellaria barbata has been used as a traditional Chinese Herb for treating liver, lung and rectal tumors. In the present study, cytotoxic effect of Scutellaria barbata MC fradtion was investigated and it was found to inhibit proliferation of human leukemic U937 cells with an IC50 of approximately 10 μg/ml in a dose-dependent manner. We also demonstrated that Scutellaria barbata MC fraction caused apoptosis in U937 cells. In the flow cytometric assay, the MC fraction-treated U937 cells showed an increase in hypo-diplold Sub G1 DNA contents. DNA fragmentation was observed by TUNEL assay. An increase of Bax:Bcl-2 ratio, activation of caspase-9, caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP) were demonstrated by western blot analysis. Taken together, these results exerted that the MC fraction suppressed human leukemic U937 cell proliferation by inducing apoptosis via the mitochondrial pathway.