• 한국식품위생안전성학회지
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• 제28권1호
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• pp.41-44
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• 2013

비록 천연유래물질 중의 하나인 통초가 항산화작용, 항염증작용 및 해열작용과 같은 효능이 있다고 알려져있지만, 종양에서의 암예방효능에 대한 연구는 보고된 바가 없다. 본 연구에서는 사람 자궁경부암세포주인 HEP-2세포에서 통초메탄올추출물의 증식억제 효능 및 관련 분자표적을 확인하고자 하였다. 통초메탄올추출물은 세포증식을 유의성있게 억제하고, 세포사멸을 유도하는 것으로 나타났다. 또한, Bid의 발현에 영향을 주어 truncation을 유도하고, 이로 인해 cytochrome c가 마이토콘드리아에서 세포질로 이동하도록 유도하였지만, Bid 이외의 다른 Bcl-2 family에는 영향을 주지 못했다. 따라서, 이러한 결과를 종합해 볼 때, 통초메탄올추출물은 자궁경부암에서 암예방효능을 가진 잠재성있는 천연추출물이 될 수 있을 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제17권3호
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• pp.282-287
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• 2009

Ochnaflavone is a natural biflavonoid and mainly found in the caulis of Lonicera japonica (Caprifoliaceae). Biological activities such as anti-inflammatory and anti-atherogenic effects have been previously reported. The anticancer activity of ochnaflavone, however, has been poorly elucidated yet. In the present study, we investigated the effect of ochnaflavone on the growth inhibitory activity in cultured human colon cancer cell line HCT-15. Ochnaflavone inhibited the proliferation of the cancer cells with an $IC_{50}$ value of $4.1{\mu}M$. Flow cytometric analysis showed that ochnaflavone arrested cell cycle progression in the G2/M phase, and induced the increase of sub-G1 peak in a concentration-dependent manner. Induction of cell cycle arrest was correlated with the modulation of the expression of cell cycle regulating proteins including cdc2 (Tyr15), cyclin A, cyclin B1 and cyclin E. The increase of sub-G1 peak by the higher concentrations of ochnaflavone (over $20{\mu}M$) was closely related to the induction of apoptosis, which was evidenced by the induction of DNA fragmentation, activation of caspase-3, -8 and -9, and cleavage of poly-(ADP-ribose) polymerase. These findings suggest that the cell cycle arrest and induction of apoptosis might be one possible mechanism of actions for the anti-proliferative activity of ochnaflavone in human colon cancer cells.

• 대한약침학회지
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• 제19권2호
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• pp.129-136
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• 2016

Objectives: The crude extracts of Scutellaria barbata D. Don (SB) have traditionally demonstrated inhibitory effects on numerous human cancers both in vitro and in vivo. Gastric cancer is one of the most common types of cancer on world. The authors investigated the effects of an ethanol extract of Scutellaria barbata D. Don (ESB) on the growth and survival of MKN-45 cells (a human gastric adenocarcinoma cell line). Methods: The MKN-45 cells were treated with different concentrations of ESB, and cell death was examined using an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Analyses of sub-G1 peaks, caspase-3 and -9 activities, and mitochondrial membrane depolarizations were conducted to determine the anti-cancer effects of SB on MKN-45 cells. Also, intracellular reactive oxygen species (ROS) generation was investigated. Results: ESB inhibited the growth of MKN-45 cells, caused cell cycle arrest, and increased the sub-G1 population. In addition, ESB markedly increased mitochondrial membrane depolarization and the activities of caspase-3 and -9. ESB exerted anti-proliferative effects on MKN-45 cells by modulating the mitogen-activated protein kinase (MAPK) signaling pathway and by increasing the generation of ROS. Furthermore, combinations of anti-cancer drugs plus ESB suppressed cell growth more than treatments with an agent or ESB, and this was especially true for cisplatin, etoposide, and doxorubicin. Conclusion: ESB has a dose-dependent cytotoxic effect on MKN-45 cells and this is closely associated with the induction of apoptosis. ESB-induced apoptosis is mediated by mitochondria-, caspase- and MAPK dependent pathways. In addition, ESB enhances ROS generation and increases the chemosensitivity of MKN-45 cells. These results suggest that treatment with ESB can inhibit the proliferation and promote the apoptosis of human gastric adenocarcinoma cells by modulating the caspase-, MAPK- and ROS-dependent pathway.

• Natural Product Sciences
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• 제18권1호
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• pp.16-21
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• 2012

Honokiol, a naturally occurring neolignan mainly found in Magnolia species, has been shown to have the anti-angiogenic, anti-invasive and cancer chemopreventive activities, but the molecular mechanism of actions has not been fully elucidated yet. In the present study, we investigated the effect of honokiol on the growth inhibitory activity in cultured SNU-638 human gastric cancer cells. We found that honokiol exerted potent antiproliferative activity against SNU-638 cells. Honokiol also arrested the cell cycle progression at the G0/G1 phase and induced the apoptotic cell death in a concentration-dependent manner. The cell cycle arrest was well correlated with the downregulation of Rb, cyclin D1, cyclin A, cyclin E, and CDK4 expression, and the induction of cyclin-dependent kinase inhibitor p27. The increase of sub-G1 peak by honokiol was closely related to the induction of apoptosis, which was evidenced by the induction of DNA fragmentation, the cleavage of poly(ADPribose) polymerase, and the sequential activation of caspase cascade. These findings suggest the cell cycle arrest and induction of apoptosis might be one possible mechanism of actions for the anti-proliferative activity of honokiol in human gastric cancer cell.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.82-82
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• 1995

4-lBB molecule is expressed on the surface of activated CD4$\^$+/ and CD8$\^$+/ T cells. We generated a panel of anti-4-1 B5 murine mAbs using a fusion protein consisting of the extracellular domain of human 4-1 BB fused to Glutathione S-transferase. The binding activity against cell surface 4-1 BB molecule was assessed by flow cytometry analysis. These studies showed that several anti-4-1 BB mAbs bound to 10-30% of CD4$\^$+/ and CD8$\^$+/T cells in PHA or Con A stimulated PBLs, although these mAbs interacted with only, l-2% of CD4$\^$+/ and CD8$\^$+/ T cells in normal PBLs, indicating the specificity of mAbs to the 4-l BB molecule on activated CD4$\^$+/ and CD8$\^$+/ T cells. Next, we examined the effect of an anti-4-l BB mAb (4B4-1-1) on allogeneic mixed lymphocyte reactions (MLRs). The data indicated that the antibody significantly inhibited the proliferative response at higher concentrations. When tested with several T cell mitogens, the antibody had no stimulatory or inhibitory effects on the mitogen-mediated T cell proliferation. These data suggest that 4-1 BB molecule may play a role in the regulation of antigen-mediated immune response.

• 한국식품영양과학회지
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• 제46권7호
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• pp.896-902
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• 2017

본 연구는 감귤 콤부차의 산업화를 위한 발효 균주 표준화를 위하여 콤부차에서 분리된 3가지 균주(Gluconacetobacter xylinus, Gluconacetobacter medellinensis, Gluconobacter oxydans)를 이용한 감귤 발효액(CK-MOX)의 기능적 특성을 탐색하고자 하였다. CK-MOX 제조 후 15일간 3일 마다 샘플링을 하였으며, 발효 기간에 따른 pH, 산도, 항산화 능력을 평가하였다. 발효에 따라 pH는 감소하였고, 산도는 증가하였다. DPPH, ABTS 라디칼 소거능, ORAC assay를 통한 항산화 능력 측정 결과 발효에 따라 항산화 능력이 향상하는 것으로 나타났으며, 방광암 세포주(EJ 세포)의 생존 억제 및 이동 억제 효과가 있는 것으로 나타났다. 특히 CK-MOX로 유도된 EJ 세포의 사멸에 MAPK pathway의 중추적인 역할을 하는 것으로 알려진 ERK의 발현이 깊이 관여하는 것으로 나타났다.

• Biomolecules & Therapeutics
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• 제23권4호
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• pp.339-344
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• 2015

Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. However, more detailed mechanism by which NAR exerts anti-cancer properties still remains unanswered. Thus, in this study, we have shown that NAR down-regulates the level of cyclin D1 in human colorectal cancer cell lines, HCT116 and SW480. NAR inhibited the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. Inhibition of proteasomal degradation by MG132 blocked NAR-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with NAR. In addition, NAR increased the phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine blocked cyclin D1 downregulation by NAR. p38 inactivation attenuated cyclin D1 downregulation by NAR. From these results, we suggest that NAR-mediated cyclin D1 downregulation may result from proteasomal degradation through p38 activation. The current study provides new mechanistic link between NAR, cyclin D1 downregulation and cell growth in human colorectal cancer cells.

• 한국식품영양학회지
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• 제22권4호
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• pp.485-491
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• 2009

In order to examine the nutritional value of prickly pear(Opuntia humifusa), contents of ash, protein, fat, minerals and vitamins were determined on freeze-dried stem, fruit, seed and root from plants harvested in autumn. The average moisture contents for stem, fruit, seed and root were 67~87%. Crude ash content determined on dry weight basis was 2~3%. Crude protein existed mostly in seed(2.95%) and root(2.37%). Crude fat was detected mainly in seed(4.49%). Contents of major minerals(mg/100 mg dry weight) was generally higher in stem. Ca in stem(4,142.30) and fruit(2,790.86) were much higher than in seed(43.37). P in stem, seed and fruit were 448.19, 263.20 and 161.59, respectively. Stem also displayed more abundant Mg(1,110.86), Zn(35.62) and Mn(37.07). However, fruit contained higher amounts of Fe(13.38) and Se(0.15). Vitamin A was negligible in all plant parts. Vitamin E contents in fruit and stem were 1.78 mg and 1.22 mg/mg dry weight, respectively. Vitamin C was detected mostly in fruit(445.40) and stem(260.94). Use of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based microtiter assay of cell viability demonstrated an anti-proliferative effect of O. humifusa extract on the MCF-7 estrogen-dependent human breast cancer cell line.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5883-5887
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• 2015

Despite recent advances in therapeutic strategies for lung cancer, mortality still is increasing. In the present study, we investigated the anti-cancer effects of KMU-193, 2-(4-Ethoxy-phenyl)-N-{5-[2-fluoro-4-(4-methylpiperazine-1-carbonyl)-phenylamino]-1H-indazol-3-yl}-acetamide in a human non-small cell lung cancer cell line A549. KMU-193 strongly inhibited the proliferation of A549 cells, but it did not have anti-proliferative effect in other types of cancer cell lines. KMU-193 further induced apoptosis in association with activation of caspase-3 and cleavage of PLC-${\gamma}1$. However, KMU-193 had no apoptotic effect in untransformed cells such as TMCK-1 and BEAS-2B. Interestingly, pretreatment with z-VAD-fmk, a pan-caspase inhibitor, strongly abrogated KMU-193-induced apoptosis. KMU-193 treatment enhanced the expression levels of p53 and PUMA. Importantly, p53 siRNA transfection attenuated KMU-193-induced apoptosis. Collectively, these results for the first time demonstrate that KMU-193 has strong apoptotic effects on A549 cells and these are largely mediated through caspase-3- and p53-dependent pathways.

• Journal of Acupuncture Research
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• 제20권3호
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• pp.45-62
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• 2003

Objective : To examine the effects of Beevenom on the cell proliferation of human breast carcinoma cell line MCF-7, we performed various experiments such as does-dependent effect of Beevenom on cell proliferation and viability, morphological changes, and alterations of apoptosis/cell cycle-regulatory gene products. Methods : Beevenom induced cell viability and proliferation of MCF-7 cells in a concentration-dependent manner. The anti-proliferative effect by Beevenom treatment in MCF-7 cells was associated with morphological changes such as membrance shrinking and cell rounding up. Results : Beevenom induced apoptotic cell death in a concentration-dependent manager, which was associated with degradation of ${\beta}$-catenin, an apoptotic target protein. Beevenom induced the Bax expressions, a pro-apoptotic gene, both in protein and mRNA levels, however, the levels of Bcl-$X_{S/L}$ expression, an anti-apoptotic gene, were down-regulated in Beevenom-treated cells. Western blot analysis and RT-PCT data revealed that the levels of cyclin of B1 protein and cyclin E mRNA were reduced by Beevenom treatment in MCF-7 cells, respectively, where as the expression of tumor suppressor p53 and cyclin dependent kinase inhibitor p21 mRNA were markedly increased in a concentration-dependent fashion. Conclusions : Taken together, these findings suggest that Beevenom induced inhibition of human breast cancer cell proliferation is associated with the induction of apoptotic cell death and Beevenom may have therapeutic potential in human breast cancer.