• Asian Pacific Journal of Cancer Prevention
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• 제17권11호
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• pp.4857-4861
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• 2016

Background: Imatinib mesylate, a tyrosine kinase inhibitor specifically targeting the BCR/ABL fusion protein, induces hematological remission in patients with chronic myeloid leukemia (CML). However, the majority of CML patients treated with imatinib develop resistance with prolonged therapy. Dendrophthoe pentandra (L.) Miq. is a Malaysian mistletoe species that has been used as a traditional treatment for several ailments such as smallpox, ulcers, and cancers. Methods: We developed a resistant cell line (designated as K562R) by long-term co-culture of a BCR/ABL positive CML cell line, K562, with imatinib mesylate. We then investigated the anti-proliferative effects of D. pentandra methanol extract on parental K562 and resistant K562R cells. Trypan blue exclusion assays were performed to determine the IC50 concentration; apoptosis and cell cycle analysis were conducted by flow cytometry. Results: D. pentandra extract had greater anti-proliferative effects towards K562R ($IC50=192{\mu}g/mL$) compared to K562 ($500{\mu}g/mL$) cells. Upon treatment with D. pentandra extract at the IC50. concentration: K562 but not K562R demonstrated increase in apoptosis and cell cycle arrest in the G2/M phase. Conclusion: D. pentandra methanol extract exerts potent anti-proliferative effect on BCR/ABL positive K562 cells.

• Journal of Microbiology and Biotechnology
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• 제12권6호
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• pp.950-956
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• 2002

The antitumor activity of the insect pathogenic fungus Paecilomyces japonica has been attributed to apoptotic cell death. However, the mechanism underlying the induced apoptosis has not yet been elucidated. In this study, we for the first time show that mitochondria-dependent caspase-3 activation were associated with the apoptotic activity of P. japonica in human acute leukemia Jurkat T cells. When Jurkat T cells were treated with the ethyl acetate extract of P japonica at concentrations ranging from $2-6{\mu}g/ml$, apoptotic cell death. accompanied by several biochemical events such as caspase-9 activation, caspase-3 activation, degradation of poly (ADP-ribose) polymerase (PARP), and apoptotic DNA fragmentation, was induced in a dose-dependent manner. In addition, the release of cytochrome c from mitochondria was detected. Under these conditions, the expression of Fas and Fas-ligand (FasL) remained unchanged. Ethyl acetate extract-induced mitochondrial cytochrome c release, caspase-3 activation, PARP cleavage, and apoptotic DNA fragmentation were suppressed by the ectopic expression of Bcl-2, which is known to block mitochondrial cytochrorme c release. Accordingly, these results demonstrate that P. japonica-induced apoptotic cell death is mediated by a cytochrome c-dependent caspase-3 activation pathway that can be interrupted by Bcl-2.

• 한국식품위생안전성학회지
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• 제26권2호
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• pp.150-153
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• 2011

흰자작나무의 껍질에서 발견된 자연적으로 발생한 triterpene 인 betulinic acid (BA)가 다양한 종류의 암세포와 동물 모델에서 세포사멸을 유도하는 것으로 알려져 있다. 하지만 자궁경부암세포에서 BA의 화학적 암예방 효과는 연구되지 않은 상태이다. 따라서 이 연구에서는 사람 자궁경부암세포주인 KB세포를 이용하여, BA가 세포증식을 감소시키고 세포사멸을 유도하는 것을 확인하였다. KB 세포에서 BA에 의해 유도되는 세포증식의 억제는 specificity protein 1 (Sp1)과 Sp1의 표적단백질인 myeloid cell leukemia-1 (Mcl-1) 그리고 survivin의 감소 때문인 것으로 확인되었다. 따라서 BA는 자궁경부암에서 과다 발현되는 Sp1을 조절하는 새로운 화학적 암예방 물질로서 작용할 수 있을 것으로 생각된다.

• 동의생리병리학회지
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• 제21권4호
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• pp.869-873
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• 2007

Methanol extracts of Acorus gramineus Solander(AGS) were found to exhibit immuno-regulatory action in BALB/c mice. Oral administration of AGS increased murine splenic T lymphocytes, especially $T_H$ and $T_C/T_S$ subpopulations were increased significantly. Treatment of AGS exerted strong cytotoxicity against U937 and HL60 human leukemia cells. Also, AGS induced apoptosis of U937 leukemia cells in a dose dependent manner. Nitric oxide(NO) production and iNOS gene expression were also increased in AGS-treated RAW264.7 cells. Treatment of AGS increased the expression of p53 gene and decreased the expression of PCNA protein in cultured U937 cells. These data suggest that AGS are effective on the immuno-regulatory action and anti-cancer properties.

• Clinical and Experimental Pediatrics
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• 제52권6호
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• pp.696-700
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• 2009

목 적 : Artemisinin은 인체에 대한 부작용이 적고 항말라리아 효능 뿐 아니라 강력한 항암효과가 있음이 알려져 있다. 저자들은 오까야마 약학대학에서 합성 된 350여개의 endoperoxide ring구조를 가진 artemisinin 유도체를 선별검사 하여 HL-60세포 주에 강력한 세포독성을 보여 준 c-127의 세포고사 유도 여부와 그 분자유전학적 기전을 알아보고자 하였다. 방 법 : HL-60세포는 RPMI 1640배지로 배양하였고 세포 생존율은 MTT분석으로 측정하였다. 세포고사 여부는 DNA추출과 전기영동법으로 확인하였으며 세포고사 유도 기전은 western blotting을 시행하여 알아보았다. 결 과 : C-127이 세포고사를 유도하여 HL-60세포의 세포 생존력을 농도 의존적으로 감소시켰다. C-127의 이런 항암효과의 분자 유전학적 기전으로는 caspase-8,3 활성화, Bcl-2 family인 Bid분절, JNK 인산화와 c-Jun 발현이 관여하였다. 결 론 : C-127이 HL-60 세포에서 세포고사를 유도하여 강력한 항암효과를 발현하였고, 그 기전으로 caspase cascade, Bcl-2 family, JNK인산화와 c-Jun활성화가 관여하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.817-824
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• 1997

Extracellular ATP elicits various biological responses and plays a significant role in physiological regulation. Recently, ATP-induced growth inhibitions were reported in some tumor cell lines, but these effects and mechanisms are not well hewn. This study was conducted to investigate ATP-induced growth inhibition in mouse $leukemic(P388D_1)$ cells. ATP inhibited cell growth in a dose-dependent manner as analyzed by MTS assay$(IC_{50}: 33.1\;{\mu}M)$. Nucleotides other than ATP, such as ADP$(37.5;{\mu}M)$ and AMP$(33.2;{\mu}M)$ had the same effects as ATP but adenosine$(57.8;{\mu}M)$ showed less effect than ATP. ATP attenuated the cells in $G_0/G_l\;and\;G_2/M$ phases but increased those in S phase in flow cytometric analysis. Hypodiploid cells$(A_0)$, the presumptive findings of apoptosis, were found among the ATP-treated cells. ATP induced DNA fragmentation into $180{\mu}200\;bps $as measured by electrophoresis. some apoptotic cells were stained by TUNEL method. ATP increased the intracellular free $Ca^{++}$concentration$([Ca^{++}]_i)$ and the increment of $([Ca^{++}]_i)$ was caused by influx from the extracellular space. These results suggest that extracellular ATP induces growth inhibition through apoptosis.

• 약학회지
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• 제53권1호
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• pp.6-11
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• 2009

This study investigated the antiproliferative effect of the EtOH extract from Litsea japonica. The extract markedly inhibited the growth of HL-60 cells. When treated with the extract, several apoptosis events like as DNA fragmentation, chromatin condensation and the increase of the population of sub-G1 hypodiploid cells were observed. The extract decreased the Bcl-2 expression, whereas the Bax expression was increased. Caspase-9 and -3 were activated and poly (ADP-ribose) polymerase was cleaved. The results suggest that the antiproliferative effect of L. japonica in HL-60 appears to arise from apoptosis induction via the down-regulation of Bcl-2 and the activation of caspases.

• Clinical and Experimental Pediatrics
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• 제60권11호
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• pp.365-372
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• 2017

Purpose: The mechanism for the pathogenesis of adriamycin (ADR)-induced cardiomyopathy is not yet known. Different hypotheses include the production of free radicals, an interaction between ADR and nuclear components, and a disruption in cardiac-specific gene expression. Apoptosis has also been proposed as being involved in cardiac dysfunction. The purpose of this study was to determine if apoptosis might play a role in ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were separated into 2 groups: the control group (C group) and the experimental group (ADR 5 mg/wk for 3 weeks through intraperitoneal injections; A group). Echocardiographic images were obtained at week 3. Changes in caspase-3, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), interleukin (IL)-6, tumor necrosis $factor-{\alpha}$, brain natriuretic peptide (BNP), troponin I, collagen 1, and collagen 3 protein expression from the left ventricle tissues of C and A group rats were determined by Western blot. Results: Ascites and heart failure as well as left ventricular hypertrophy were noted in the A group. Ejection fraction and shortening fraction were significantly lower in the A group by echocardiography. The expression of caspase-3, Bax, IL-6, BNP, collagen 1, and collagen 3 were significantly higher in the A group as compared with the C group. Protein expression of Bcl-2 decreased significantly in the A group compared with the C group. Conclusion: ADR induced an upregulation of caspase-3, Bax, IL-6, and collagen, as well as a depression in Bcl-2. Thus, apoptosis and fibrosis may play an important role in ADR-induced cardiomyopathy.

• International Journal of Oral Biology
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• 제42권1호
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• pp.17-23
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• 2017

Background: Periodontitis is generally a chronic disorder characterized by the breakdown of tooth-supporting tissues. P. gingivalis, a Gram-negative anaerobic rod, is one of the major pathogens associated with periodontitis. Frequently, P. gingivalis infection leads to cell death. However, the correlation between P. gingivalis-induced cell death and periodontal inflammation remains to be elucidated. Among cell deaths, the death of immune cells appears to play a significant role in inflammatory response. Thus, the aim of this study was to examine P. gingivalis-induced cell death, focusing on autophagy and apoptosis in THP-1 cells. Methods: Human acute monocytic leukemia cell line (THP-1) was used for all experiments. Autophagy induced by P. gingivalis in THP-1 cells was examined by Cyto ID staining. Intracellular autophagic vacuoles were observed by fluorescence microscopy using staining Acridine orange (AO); and 3-methyladenine (3-MA) was used to inhibit autophagy. Total cell death was measured by LDH assay. Cytokine production was measured by an ELISA method. Results: P. gingivalis induced autophagy in an MOI-dependent manner in THP-1 cells, but 3-MA treatment decreased autophagy and increased the apoptotic blebs. P. gingivalis infection did not increase apoptosis compared to the control cells, whereas inhibition of autophagy by 3-MA significantly increased apoptosis in P. gingivalis-infected THP-1 cells. Inhibition of autophagy by 3-MA also increased total cell deaths and inflammatory cytokine production, including $IL-1{\beta}$ and $TNF-{\alpha}$. Conclusion: P. gingivalis induced autophagy in THP-1 cells, but the inhibition of autophagy by 3-MA stimulated apoptosis, leading to increased cell deaths and pro-inflammatory cytokines production. Hence, the modulation of cell deaths may provide a mechanism to fight against invading microorganisms in host cells and could be a promising way to control inflammation.

• Archives of Pharmacal Research
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• 제25권2호
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• pp.191-196
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• 2002

The water extract from the root bark of Cortex Mori (CM, Morus alba L.: Sangbaikpi), a mulberry tree, has been known in Chinese traditional medicine to have antiphlogistic, diuretic, and expectorant properties. In this study, the cytotoxicity of CM against tumor cells and its mechanism was examined . CM exhibited cytotoxic activity on K-562, B38O human leukemia cells and B16 mouse melanoma cells at concentrations of > 1 mg/ml. A DNA fragmentation, PARP cleavage, and nuclear condensation assay showed that those cells exposed to CM underwent apoptosis. The water extract of Scutellarie Radix (SR) was used as a negative control and showed no cytotoxicity in those cells. The flow cytometric profiles of the CM-treated cells were also indicative of apoptosis. However, they did not appear to exert the G1 arrest, which is observed in other tubulin inhibitor agents such as vincristine, taxol. The protein-binding test using Biacore and a microtubule assembly-disassembly assay provided evidence showing that CM bound to the tubulins resulting in 3 markets inhibition of the assembly, but not the disassembly of microtubules. The possible nonspecific effect of the CM extract could be excluded due to the results using SR, which did not affect the assembly process. Overall, the water extract of CM induces apoptosis of tumor cells by inhibiting microtubule assembly.