• The Korean Journal of Physiology and Pharmacology
• /
• 제14권6호
• /
• pp.407-412
• /
• 2010

3-Deazaadenosine (DZA), a potent inhibitor of S-adenosylhomocysteine hydrolase, was previously proposed to induce intrinsic apoptosis in human leukemic cells. In the present study, we analyzed the mechanism underlying the DZA-induced intrinsic apoptotic pathway. DZA activated typical caspase-dependent apoptosis in HL-60 cells, as demonstrated by an accumulation of hypo-diploidic cells, the processing of multiple procaspases and an inhibitory effect of z-VAD-Fmk on this cell death. During DZA-induced apoptosis, cytochrome c (cyt c) was released into the cytosol. This was neither prevented by z-VAD-Fmk and nor was it associated with the dissipation of mitochondrial membrane potential (${\Delta}{\Psi}_m$). Prior to the release of cyt c, BAX was translocated from the cytosol to mitochondria and underwent oligomerization. Finally, the overexpression of BCL-XL protected HL-60 cells from apoptosis by blocking both the cyt c release and BAX oligomerization. Collectively, these findings suggest that DZA may activate intrinsic apoptosis by stimulating BAX activation and thereby the release of cyt c.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권12호
• /
• pp.7719-7724
• /
• 2013

Background: Overexpression of survivin, a known inhibitor of apoptosis, is associated with tumor progression and drug resistance in numerous malignancies, including leukemias. The aim of this study was to investigate the effect of a specific survivin small interference RNA (siRNA) on proliferation and the sensitivity of HL-60 acute myeloid leukemia (AML) cells to the chemotherapeutic drug etoposide. Materials and Methods: The cells were transfected with siRNAs using Lipofectamine $^{TM}2000$ transfection reagent. Relative survivin mRNA and protein levels were measured by quantitative real-time PCR and Western blotting, respectively. Trypan blue exclusion assays were performed to monitor tumor cell proliferation after siRNA transfection. The cytotoxic effects of etoposide and survivin siRNA, alone and in combination, on leukemic cells were determined using MTT assay. Apoptosis was assessed by ELISA cell death assay. Results: Survivin siRNA markedly reduced both mRNA and protein expression levels in a time-dependent manner, leading to distinct inhibition of cell proliferation and increased spontaneous apoptosis. Surprisingly, survivin siRNA synergistically increased the cell toxic effects of etoposide. Moreover, survivin down-regulation significantly enhanced its induction of apoptosis. Conclusions: Our study suggests that down-regulation of survivin by siRNA can trigger apoptosis and overcome drug resistance of leukemia cells. Therefore, survivin siRNA may be an effective adjuvant in AML chemotherapy.

• Advances in Traditional Medicine
• /
• 제7권4호
• /
• pp.341-347
• /
• 2007

Red seaweed (Callophyllis japonica) has long formed part of the diet of Asians, but the pharmacological properties of this plant have not been evaluated. In this study, we examined the effect of an ethanol extract of C. japonica on the generation of nitric oxide (NO) in RAW 264.7 cells. The C. japonica extract increased the generation of NO and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), which were detected by the Griess method and an enzyme-linked immunosorbent assay, respectively. The increased production of NO by C. japonica extract was inhibited by $N^G$-monomethyl-L-arginine ($100{\mu}M$), a specific inhibitor of NO production in the L-arginine-dependent pathway, and by the nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) inhibitor, pyrrolidine dithiocarbamate ($10-100{\mu}M$) in a dose-dependent manner. These findings demonstrate that C. japonica extract stimulates the production of NO and $TNF-{\alpha}$ in RAW 264.7 cells through the activation of $NF-{\kappa}B$ and that this extract might also inhibit the growth of the human leukemic cells.

• 생명과학회지
• /
• 제18권1호
• /
• pp.96-102
• /
• 2008

이상의 연구 결과에 의하면 piceatannol의 처리에 의한 U937 세포의 증식억제는 세포주기 S기 arrest 및 apoptosis 유발과 뚜렷한 연관성이 있었다. 또한 piceatannol은 hTERT 및 TEP-1 유전자의 발현 저하와 연관된 telomerase 활성의 저하 효과도 나타내었으나, COXs의 발현 및 PGE2의 생성에는 큰 변화를 주지 못하였다. 따라서 본 연구의 결과는 암세포에서 높게 발현되는 telomerase 활성 조절제로서 piceatannol의 적용이 가능함을 보여주며, 이는 piceatannol의 항암작용을 이해하는데 매우 유용한 자료라 생각한다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제16권1호
• /
• pp.31-36
• /
• 2012

The receptor activator of NF-${\kappa}B$ ligand (RANKL) signal is an activator of tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the activation of NF-${\kappa}B$ and other signal transduction pathways essential for osteoclastogenesis, such as $Ca^{2+}$ signaling. However, the intracellular levels of inositol 1,4,5-trisphosphate ($IP_3$) and $IP_3$-mediated cellular function of RANKL during osteoclastogenesis are not known. In the present study, we determined the levels of $IP_3$ and evaluated $IP_3$-mediated osteoclast differentiation and osteoclast activity by RANKL treatment of mouse leukemic macrophage cells (RAW 264.7) and mouse bone marrow-derived monocyte/macrophage precursor cells (BMMs). During osteoclastogenesis, the expression levels of $Ca^{2+}$ signaling proteins such as $IP_3$ receptors ($IP_3Rs$), plasma membrane $Ca^{2+}$ ATPase, and sarco/endoplasmic reticulum $Ca^{2+}$ ATPase type2 did not change by RANKL treatment for up to 6 days in both cell types. At 24 h after RANKL treatment, a higher steady-state level of $IP_3$ was observed in RAW264.7 cells transfected with green fluorescent protein (GFP)-tagged pleckstrin homology (PH) domains of phospholipase C (PLC) ${\delta}$, a probe specifically detecting intracellular $IP_3$ levels. In BMMs, the inhibition of PLC with U73122 [a specific inhibitor of phospholipase C (PLC)[ and of $IP_3Rs$ with 2-aminoethoxydiphenyl borate (2APB; a non-specific inhibitor of $IP_3Rs$) inhibited the generation of RANKL-induced multinucleated cells and decreased the bone-resorption rate in dentin slice, respectively. These results suggest that intracellular $IP_3$ levels and the $IP_3$-mediated signaling pathway play an important role in RANKL-induced osteoclastogenesis.

• Journal of Nutrition and Health
• /
• 제39권4호
• /
• pp.347-356
• /
• 2006

It is reported that a fermented soybean food, Doenjang, has srong antimutagenic and cytotoxic effect on cancer cells. This study investigated the effect of Chungkookjang, another traditional popular Korean soybean fermented food, on growth of cancer cells: HL-60, SNU-638 and MCF-7, and also its in vivo antitumorigenic effect in DMBA-induced mammary tumor rat model. For the in vitro study, Chungkookjang and steamed soybeans were extracted with ethanol and sequentially fractioned with 5 kinds of solvents differing in grades of polarity such as hexane, dichloromethane, ethylacetate, butanol and water. Almost all Chungkookjang extracts significantly inhibited the growth of HL-60 (human leukemic cancer cell), SNU-638 (human gastric cancer cell) and MCF-7 (human breast cancer cell) when compared to steamed soybean extracts. Butanol fraction of Chungkookjang extract especially showed a remarkable inhibitory effect in all the three kinds of cancer cells. To induce a mammary gland tumor, DMBA (50 mg/BW) was administered to 50 day-old female rats and followed by Chungkookjang or steamed soybean supplemented diets. Freezedried Chungkookjang powder (20% of diet in wet weight) was added to AIN-93G based diet for the Chungkookjang group of rats. Likewise, steamed soybean powder containing equal protein content to that of Chungkookjang powder was supplemented to soybean group of rats. At 13 weeks later, the mammary tumor incidence, average tumor number and tumor weight a rat were lower in Chungkookjang group compared to the control or soybean group. In conclusion, Chungkookjang showed a strong inhibitory effect on cancer cell growth in vitro, as well as a more preventive effect against chemically induced mammary tumorigenesis in vivo, while steamed soybeans did not. Therefore, these results suggest that Chungkookjang acquire its anticancer activity through the fermentation process.

• 대한의생명과학회지
• /
• 제3권2호
• /
• pp.71-76
• /
• 1997

실험적 자궁암 치료제로서 본 연구소에서 합성한 마이토센유사체를 인체 자궁암세포주인 SiHa, C33A, HeLa, CaSki에 처리하여, 체외 항암활성 측정시 합성 마이토센유사체들은 이 들 세포주에 대하여 대조 항암제들에 비하여 의의있는 세포독성을 보였으며, SiHa 세포주를 이용한 종양클론형성 억제검사에서는 22번 화합물만이 종양성장 억제활성이 가장 우수하였고 다른 화합물들은 대조항암제들에 비하여 활성이 낮았다. 이 마이토센유사체들에 대한 체외 항암감수성결과는 향후 전임상적인 자궁경부암 화합요법제의 기초자료로 유용할것으로 생각된다.

• 대한본초학회지
• /
• 제28권6호
• /
• pp.155-160
• /
• 2013

Objectives : Gastric cancer is a leading cause of cancer-related deaths, worldwide. Houttuynia cordata Thunberg (H. cordata) has been used as a medicinal plants and it has an anti-cancer activity in human colorectal cancer and leukemic cancer. However, the potential anti-cancer activity and mechanisms of H. cordata for human gastric cancer cells have not been tested so far. Thus, this study examined the biological effects of H. cordata on the human gastric cancer cell line SNU-1 and AGS. Methods : Inhibition of cell proliferation and cell cycle by H. cordata was carried out by MTT assay and Muse cell cycle analysis and the expressions of protein associated with apoptosis and cell cycle regulation were investigated with Western blot analysis. Results : In MTT assay, the proliferation of SNU-1 and AGS cells was significantly inhibited by H. cordata in a time and dose dependent manner, Inhibition of cell proliferation by H. cordata was in part associated with apoptotic cell death, as shown by changes in the expression ratio of Bax to Bcl-2 by H. cordata. Also, H. cordata regulated the expression of cell cycle regulatory proteins such as pRb, cyclin D1, cyclin E, CDK4, CDK2, p21 and p15. Conclusion : The antiproliferative effect of H. cordata on SNU-1 and AGS gastric cancer cells revealed in this study suggests that H. cordata has intriguing potential as a chemopreventive or chemotherapeutic agent.

• 한국미생물·생명공학회지
• /
• 제10권1호
• /
• pp.53-58
• /
• 1982

천연물 가운데서 항암물질을 얻을 목적으로 동양에서 오랫동안 암이나 암에 비슷한 질병의 치료에 씌여온 한약재를 물이나 유기용매로서 추출하여 검색하였다. Fischer배지에 자라는 L1210 세포에 추출물을 첨가한 다음 48시간 후에 세포수를 헤아려 생장을 50% 억제할 수 있는 추출물의 농도를 나타내는 ED$_{50}$값을 측정하였다. 물로서 추출한 38종의 한약재 가운데서 6종이 낮은 ED$_{50}$값을 나타냈다. 이들을 다시 유기용매로서 추출하므로써 ED$_{50}$값이 더욱 떨어져 NCI의 품질관리범위 치역내에 들어갔다. 항암제원으로 유망시되는 한약재로서 Cinnamomum cassia, Citrus trifoliata, Coptis japonica, Panax ginseng, Phellodendron amurense, Scutellaria baikalensis를 들 수가 있다.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제31권6호
• /
• pp.535-540
• /
• 2009

Proliferation of abnormal hematopoietic cells with impaired differentiation, regulation and programmed cell death leads to leukemia. AML(acute myeloid leukemia) is a malignancy with malfunction of myeloid hematopoietic cells with acute behavior. The oral manifestations of the disease are posterior palate hemorrhage, gingival bleeding and gingival ulceration as a result of infection by normal oral flora and gingival infiltration by leukemic cells. A 49-year-old male patient was referred from local dental clinic. The patient was diagnosed with AML FAB M1 (acute myeloid leukemia French-American-British classification M1 myeloblastic leukemia without maturation). The oral infection focus was removed by a conservative treatment. 2 days after the dental treatment, the patient underwent chemotherapy. At 8-month follow-up, the overall outcome was excellent. Oral manifestations of AML are often the first indications of the malignancy. Therefore it is essential for dentists, especially oral and maxillofacial surgeons, to be aware of the diagnostic signs and complications associated with leukemia for better diagnosis and subsequent treatment and management.