• BMB Reports
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• 제31권4호
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• pp.333-338
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• 1998

The sphingomyelin cycle and ceramide generation have been recognized as potential growth suppression signals in mammalian cells. Ceramide has been shown to induce differentiation, cell growth arrest, senescence, and apoptosis. Although the intracelluar target for the action of ceramide remains unknown, recent studies have demonstrated the role of cytosolic ceramideactivated protein phosphatase(CAPP). In this study, the cytotoxic effect of C2-ceramide, a synthetic cellpermeable ceramide analog, on HEp-2 cells and the mechanism by which ceramide induces cell death were investigated. The addition of exogenous C2-ceramide resulted in a concentration dependent cell death. Okadaic acid, a potent inhibitor of CAPP, enhanced ceramide-mediated cell death, which suggests that CAPP is not involved in this process. To understand the mechanism of action of ceramide, we studied the relationship between ceramide and c-Myc and pRb which are defined components of cell growth regulation. Western blot analyses revealed that C2-ceramide (10${\mu}M$) induced c-Myc down-regulation, but there were no significant changes in pRb. However, treatment of okadaic acid (10 nM) enhanced c-Myc and pRb down-regulation. Reduction of the amount of c-Myc and pRb occurred during HEp-2 cell death. These results suggest that the cytotoxic effect of ceramide in HEp-2 cells may not be mediated through the action of CAPP and that the downstream target for ceramide is c-Myc and pRb.

• Journal of Pharmaceutical Investigation
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• 제34권1호
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• pp.23-27
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• 2004

The urushiol-ethanol corpuscle of 320 nM in average particle size was prepared and concentrated by ultra homogenization and centrifugation. The cytotoxic profiles of this particle for use as anti-tumor agent have been evaluated in vitro in cultures of human fibroblasts (MRC-9) and celvical carcinoma cells (CUMC-3). The cytotoxicty assays revealed that the inhibitor effect of $10^{-5}$ M urushiol-ethanol particle on the growth of MRC-9 was hardly detected, while CUMC-3 cells exhibited over 50% of growth inhibition under the same conditions. In addition, a clear multiple-unit ladder pater of apoptotic DNA was observed for the urushiol treated CUMC-3 cells. Thus, the results indicated that urushiol inhibited growth of celvical carcinoma cells by inducing apoptosis, which is a mechanism observed with other typical antitumor agents.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8313-8319
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• 2016

We have recently shown that thymoquinone (TQ) has a potent cytotoxic effect and induces apoptosis via caspase-3 activation with down-regulation of XIAP in mouse neuroblastoma (Neuro-2a) cells. Interestingly, our results showed that TQ was significantly more cytotoxic towards Neuro-2a cells when compared with primary normal neuronal cells. In this study, the effects of TQ on cell-cycle regulation and the mechanisms that contribute to this effect were investigated using Neuro-2a cells. Cell-cycle analysis performed by flow cytometry revealed cell-cycle arrest at G2/M phase and a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Moreover, TQ increased the expression of p53, p21 mRNA and protein levels, whereas it decreased the protein expression of PCNA, cyclin B1 and Cdc2 in a dose-dependent manner. Our finding suggests that TQ could suppress cell growth and cell survival via arresting the cell-cycle in the G2/M phase and inducing apoptosis of neuroblastoma cells.

• Food Science and Biotechnology
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• 제15권6호
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• pp.937-941
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• 2006

Chitosan has a wide range of applications in biomedical materials as well as in dietary supplements. Chitosan oligosaccharide with free-amine group (COFa) is an improvement over traditional chitosan that lacks the usual impurities and materials detrimental to the body. Based on a previous study of water soluble chitosan (WSC, chitosan lactate), we investigated the molecular weight (Mw) - dependent absorption phenomena of COFa in vitro and in vivo with various Mws. The absorption of CO Fa was significantly influenced by its molecular weight. As Mw increases, the absorption decreases. The absorption profiles for 5 K COFa (Mw=5 kDa) were observed to be more than 10 times higher than those of high molecular weight chitosan (100 K HWSC Mw=100 kDa) in both in vitro and in vivo transport experiments. Furthermore, the in vitro transport experiment suggested that transcellular transport of the COFa (Mw <10 kDa) through Caco-2 cell layer could occur with a negligible cytotoxic effect. The COFas showed a cytotoxic effect on Caco-2 cells that was dependent on dose and Mw. COFa could be transported transcellularly through the Caco-2 cell layer.

• Journal of Microbiology and Biotechnology
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• 제18권12호
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• pp.1997-2003
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• 2008

Cordyceps militaris is well known as a traditional medicinal mushroom and has been shown to exhibit immunostimulatory and anticancer activities. In this study, we investigated the apoptosis induced by an aqueous extract of C. militaris (AECM) via the activation of caspases and altered mitochondrial membrane permeability in human breast cancer MDA-MB-231 cells. Exposure to AECM induced apoptosis, as demonstrated by a quantitative analysis of nuclear morphological change and a flow cytometric analysis. AECM increased hyperpolarization of mitochondrial membrane potential and promoted the activation of caspases. Both the cytotoxic effect and apoptotic characteristics induced by AECM treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role of caspase-3 in the observed cytotoxic effect. AECM-induced apoptosis was associated with the inhibition of Akt activation in a time-dependent manner, and pretreatment with LY294002, a PI3K/Akt inhibitor, significantly increased AECM-induced apoptosis. The results indicated that AECM-induced apoptosis may relate to the activation of caspase-3 and mitochondria dysfunctions that correlate with the inactivation of Akt.

• 대한한방내과학회지
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• 제29권1호
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• pp.25-31
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• 2008

Objectives : The study was intended to investigate whether Iljoong-eum (IJE) significantly affects proliferation and growth of prostate cancer cells. Materials and Methods : In vitro, after the treatment of DU-145 and PC-3 cells with IJE, we performed Sulforhodamine B (SRB) method. In vivo, a total of 8 male nude mice subcutaneously transplanted with the PC-3 cell line were divided in 2 groups. An experimental group was given IJE orally at a dose of 4.29ml/kg per day from the 8th to 31st day following tumor injection. All mice were observed for 31 days, and sacrificed by CO2 gas asphyxiation at the end of the experiment. The mean tumor volume and body weight of both groups were compared using Student's t-tests. Results : In vitro, IJE inhibited significantly proliferation and growth of DU-145 cells and PC-3 cells. In vivo, IJE inhibited significantly proliferation and growth of PC-3 cells xenografted into athymic nude mice. Conclusions : Our data has shown that IJE is effective in suppressing the growth rate of prostate cancer cells.

• Toxicological Research
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• 제19권4호
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• pp.293-296
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• 2003

The effect of the hexane extract of Curcuma zedoaria roots and its solvent fractions were investigated on the proliferation of SiHa, SNU-1 and HepG2 cell lines. Among those fractions, final fraction H2-3-1 and H2-3-3 showed cytotoxic effect on SiHa and HepG2 cell lines. The hallmark of apoptosis, DNA fragmentation, also appeared in the final fractions H2-3-1 and H2-3-3 after 24h treatment in SiHa cell line. Furthermore, those fractions were shown to be able to induce cell death in $[^3H]$thymidine incorporation test. These two fractions, H2-3-1 and H2-3-3 were determined as (-)-$\alpha$-curcumene and $\beta$-tumerone respectively by NMR and mass spectrum. From these results, it is speculated that te hexane extract of Curcuma zedoaria is necessary for further studies as a potent inhibitor of the growth of cancer cells.

• 동의생리병리학회지
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• 제19권4호
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• pp.1011-1015
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• 2005

Antitumor and anti-metastatic effects of mineral powder(MP) were studied. In the present study, MP did not exhibit the any cytotoxic activity against leukemic cells such as L1210 and U937 tumor cell lines in vitro. Also, MP did not exhibit the any cytotoxic activity against solid cells such as A549 and B16-BL6 tumor cell lines in vitro. However, in vivo, MP exhibit a significant antitumor activity in BDF1 mice bearing Lewis lung carcinoma cells(LLC) with inhibition rates of 46 and $23\%$ at 200 and 100 mg/kg/day, respectively. Furthermore, in pulmonary colonization assay, MP exhibit the inhibitory effect of tumor metastasis. From these results, it was concluded that MP had antitumor and anti-metastatic activity suggesting its application for the prevention and treatment of cancer.

• Food Science and Biotechnology
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• 제16권6호
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• pp.1029-1034
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• 2007

Curcumin (diferuloyl methane), originated rhizomes of Curcuma longa L. has been suggested as an anti-inflammatory and anti-carcinogenic agent. In the present study, modulation of cytotoxic effects of curcumin on HeLa cells by different types of antioxidants was investigated. Cytotoxic effects of curcumin were significantly enhanced in the presence of superoxide dismutase (SOD) by decreasing $IC_{50}$ to 15.4 from $26.0\;{\mu}M$ after 24 hr incubation; the activity was not altered by catalase. The effect of curcumin was significantly less pronounced in the presence of 4 mM N-acetylcysteine (NAC). Low concentration (<1 mM) of NAC, however, increased the efficacy of curcumin. Cysteine and ${\beta}$-mercaptoethanol that have a thiol group, showed the similar biphasic patterns as NAC for modulating curcumin cytotoxicity, which was, however, constantly enhanced by ascorbic acid, a non-thiol antioxidant. In the presence of SOD, ascorbic acid, and 0.5 mM NAC, cellular levels of curcumin were significantly increased by 31-66%, whereas 4 mM NAC decreased the level. The present results indicate that thiol reducing agents showed a biphasic effect in modulating cytotoxicity of curcumin; it is likely that their thiol group is reactive with curcumin especially at high concentrations.

• 한국자원식물학회지
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• 제10권4호
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• pp.346-350
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• 1997

식용 및 약용작물중에서 암세포에 대하여 생체세포독성을 유발하는 소재를 선발하기 위하여 한국인종양에서 유래한 대장암세포주(SNU-C4)와 위아세포주(SNU-1)에 대해 MTT검색법으로 50% 세포성장저해농도($IC_{50}$)를 측정한 결과는 다음과 같다. 1. 암세포에 대해 생체세포독성활성을 가지는 작물을 선발하기 위하여 17종의 작물을 대상으로 검색한 결과 보리, 옥수수, 오미자에서 세포독성효과가 $230{\mu}g/ml$이하의 농도로 유의한 효과를 나타내었다. 2. 품종간의 세포독성효과의 차이를 검색하기 위하여 세포독성효과를 나타낸 작물중에서는 보리와 옥수수를, 세포독성효과를 미약하게 나타내거나 나타내지 않은 작물중에서는 벼와 귀리를 대상으로 품종별로 검색한 결과, 세포독성의 유무는 1차 검색과 동일한 경향이 나타났으나, 벼에서는 품종에 따라 현저하게 세포독성의 차이를 나타내었으며, 특이할만한 점은 유색미인 흑도에서 다른 품종에 비하여 50% 세포성장저해농도가 유의하게 낮게 나타났다.