• Natural Product Sciences
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• 제21권4호
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• pp.282-288
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• 2015

Viriditoxin is a fungal metabolite isolated from Paecilomyces variotii, which was derived from the giant jellyfish Nemopilema nomurai. Viriditoxin was reported to inhibit polymerization of FtsZ, which is a key protein for bacterial cell division and a structural homologue of eukaryotic tubulin. Both tubulin and FtsZ contain a GTP-binding domain, have GTPase activity, assemble into protofilaments, two-dimensional sheets, and protofilament rings, and share substantial structural identities. Accordingly, we hypothesized that viriditoxin may inhibit eukaryotic cell division by inhibiting tubulin polymerization as in the case of bacterial FtsZ inhibition. Docking simulation of viriditoxin to ${\beta}-tubulin$ indicated that it binds to the paclitaxel-binding domain and makes hydrogen bonds with Thr276 and Gly370 in the same manner as paclitaxel. Viriditoxin suppressed growth of A549 human lung cancer cells, and inhibited cell division with G2/M cell cycle arrest, leading to apoptotic cell death.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7527-7532
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• 2014

Saussurea involucrata is a Mongolian medicinal plant well known for its effects in promoting blood circulation, and anti-inflammation and analgesic functions. Earlier studies reported that Saussurea involucrata has anticancer activity. The purpose of this study was to confirm the anticancer activity of an ethanol extract of Saussurea involucrata against hepatic cancer and elucidate its mechanisms of action. Hepatocellular carcinoma cells were tested in vitro for cytotoxicity, AO/EB staining for apoptotic cells, apoptotic DNA fragmentation and cell cycle distribution in response to Saussurea involucrata extract (SIE). The mRNA expression of caspase-3,-9 and Cdk2 and protein expression of caspase-3,-9, PARP, XIAP, Cdk2 and p21 were analyzed through real time PCR and Western blotting. Treatment with SIE inhibited HepG2 cell proliferation dose- and time-dependently, but SIE only exerted a modest cytotoxic effect on a viability of Chang human liver cells. Cells exposed to SIE showed typical hallmarks of apoptotic cell death. Cell cycle analysis revealed that SIE caused G1-phase arrest in HepG2 cells. In conclusion, Saussurea involucrata ethanol extract has potential cytotoxic and apoptotic effects on human hepatocellular carcinoma cells. Its mechanism of action might be associated with the inhibition of DNA synthesis, cell cycle (G1) arrest and apoptosis induction through up-regulation of the protein expressions of caspase-3,-9 a nd p21, degradation of PARP and down-regulation of the protein expression of Cdk2 and XIAP.

• KSBB Journal
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• 제30권5호
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• pp.223-229
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• 2015

In this study, extract from Artemisia annua in L. (AAE) is known as a medicinal herb that is effective against cancer. The cell cycle is regulated by the activation of cyclin-dependent kinase (CDK)/cyclin complex. We will focus on regulation of CDK2 by cyclin E. cyclin E is associated with CDK2 to regulate progression from G1 into S phase. Akt is known to play an important role in cell proliferation and cell survival. Activation of Akt increases mTOR activity that promotes cell proliferation and cancer growth. In this study, we investigated that AAE-induced cell cycle arrest at G1/S phase in HCT116 colon cancer. Treatment of AAE shows that reduced activation of Akt decreases mTOR/Mdm2 activity and then leads to increase the activation of p53. The active p53 promotes activation of p21. p21 induces inactivation of CDK2/cyclin E complex and occurs cell cycle arrest at G1/S phase. We treated LY294002 (Akt inhibitor) and Rapamycin (mTOR inhibitor) to know the relationship between the signal transduction of proteins associated with cell cycle arrest. These results suggest that AAE induces cell cycle arrest at G1/S phase by Akt/mTOR pathway in HCT116 colon cancer cell.

• 생명과학회지
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• 제17권12호
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• pp.1709-1716
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• 2007

본 연구에서는 몇 가지 암세포를 대상으로 마늘 열수추출물(WEAS)의 항암활성을 조사하였으며, 비교적 높은 감수성을 보인 백혈병세포를 대상으로 세포증식억제가 apoptosis 유도와 연관성이 있음을 제시하였다. WEAS에 의한 U937 세포의 apoptosis 유도는 세포주기 G2/M arrest와 연관성이 있었으며, 다양한 apoptosis조절 유전자들의 발현 변화를 동반하였음을 확인하였다. 이러한 apoptosis조절 인자들의 발현변화는 미토콘드리아 막 전위의 소실과 연관성이 있었으며, WEAS에 의한 암세포의 G2/M arrest에 의한 apoptosis 유발에 ROS가 중요한 조절자로 작용함을 알 수 있었다.

• Nutrition Research and Practice
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• 제9권2호
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• pp.111-116
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• 2015

BACKGROUND/OBJECTIVES: Inonotus obliquus (I. obliquus, Chaga mushroom) has long been used as a folk medicine to treat cancer. In the present study, we examined whether or not ethanol extract of I. obliquus (EEIO) inhibits cell cycle progression in HT-29 human colon cancer cells, in addition to its mechanism of action. MATERIALS/METHODS: To examine the effects of Inonotus obliquus on the cell cycle progression and the molecular mechanism in colon cancer cells, HT-29 human colon cancer cells were cultured in the presence of $2.5-10{\mu}g/mL$ of EEIO, and analyzed the cell cycle arrest by flow cytometry and the cell cycle controlling protein expression by Western blotting. RESULTS: Treatment cells with $2.5-10{\mu}g/mL$ of EEIO reduced viable HT-29 cell numbers and DNA synthesis, increased the percentage of cells in $G_1$ phase, decreased protein expression of CDK2, CDK4, and cyclin D1, increased expression of p21, p27, and p53, and inhibited phosphorylation of Rb and E2F1 expression. Among I. obliquus fractions, fraction 2 (fractionated by dichloromethane from EEIO) showed the same effect as EEIO treatment on cell proliferation and cell cycle-related protein levels. CONCLUSIONS: These results demonstrate that fraction 2 is the major fraction that induces $G_1$ arrest and inhibits cell proliferation, suggesting I. obliquus could be used as a natural anti-cancer ingredient in the food and/or pharmaceutical industry.

• Molecules and Cells
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• 제20권3호
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• pp.331-338
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• 2005

Ionizing radiation and doxorubicin both produce oxidative damage and double-strand breaks in DNA. Double-strand breaks and oxidative damage are highly toxic and cause cell cycle arrest, provoking DNA repair and apoptosis in cancer cell lines. To investigate the response of normal human cells to agents causing oxidative damage, we monitored alterations in gene expression in F65 normal human fibroblasts. Treatment with ${\gamma}$-irradiation and doxorubicin altered the expression of 23 and 68 known genes, respectively, with no genes in common. Both agents altered the expression of genes involved in cell cycle arrest, and arrested the treated cells in $G_2M$ phase 12 h after treatment. 24 h after ${\gamma}$-irradiation, the percentage of $G_1$ cells increased, whereas after doxorubicin treatment the percentage of $G_2M$ cells remained constant for 24 h. Our results suggest that F65 cells respond differently to ${\gamma}$-irradiation- and doxorubicin-induced DNA damage, probably using entirely different biochemical pathways.

• Radiation Oncology Journal
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• 제16권2호
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• pp.91-98
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• 1998

목적 : SCK 선암 세포주에서 방사선 조사에 의해 일어나는 apoptosis와 세포 주기와의 연관성을 규명하고자하였다. 대상 및 방법 : SCK 선암 세포주를 apoptosis의 통상적인 정성 분석 방법인 agarose gel electrophoresis 방법을 이용하여 방사선 조사량과 배지 pH 환경과의 연구에서 2-l2Gy의 방사선 조사량과 pH 7.5 및 5.6의 배양 배자 조건하에서 다양한 배양 시간의 경과에 따른 DNA fragmentation의 지표인 laddering을 관찰하였다. 실험 조작으로 apoptosis가 유발된 세포군을 정량적으로 분석하고 세포 주기 분석을 위해 FACScan을 이용하였다. 결과 : apoptosis가 왕성히 발현되었던 pH 7.5 배지에서 배양하였던 세포에서는 방사선 조사직후부터 $G_2M$ phase의 세포들의 분획이 증가하기 시작하여 12시간째 약 $70\%$까지의 최고치를 보인 후 36시간째에 방사선을 조사하지 않았던 상태의 분획으로 정상화되었다. 하지만 pH 6.6 배지에서 배양하였던 세포에서의 $G_2/M$ phase의 세포들의 분획의 증가는 pH 7.5 배지에서 배양하였던 세포들에 비해 비교적 천천히 일어나고 그 최고치도 24시간째에 약 $45\%$로 관찰되었다. 특이한 것은 $G_2/M$ phase의 세포들의 분획이 그 이후 감소되는 정도가 pH 7.5 배지에서 배양하였던 세포들에 비해 미약하여 48시간 배양 이후에도 약 $30-35\%$의 세포는 $G_2/M$ Phase의 세포들의 분획으로 관찰되었다. 결론 : 연구자들은 이러한 현상이 세포들이 GJM phase에서 많은 양의 세포들이 집적되어 세포주기를 순환하지 못하는 $G_2M$ arrest 현상으로 이해하였다. 세포 내외의 산성환경 상태에서 방사선을 조사 받은 SCK 종양세포는 $G_2/M$ arrest 상태가 지속되며 이는 post-mitotic apoptosis를 억제한다고 추론하였다.

• 한국미생물생명공학회:학술대회논문집
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• 한국미생물생명공학회 2001년도 Proceedings of 2001 International Symposium
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• pp.99-99
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• 2001

• 한방안이비인후피부과학회지
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• 제32권4호
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• pp.1-12
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• 2019

Objectives : The purpose of this study was to identify the anticancer effect of biological substances of ethylacetate(EtOAc) fraction from Orostachys japonicus(OJEF), their effect on human melanoma A375 cells and the related molecular mechanisms. Methods : The MTS assay was used to confirm the inhibition of cancer cell proliferation in A375 cells. And the $MUSE^{TM}$ analyzer was used to determine the ability of OJEF to induce cell cycle arrest. Western blotting was used to determine the changes in protein expression in A375 cells after treatment with OJEF. Results : OJEF showed cytotoxicity to A375 cells. And cell cycle arrest occurred in G1 phase and G2/M phase owing to inhibition of CDK1, cyclin B1, CDK4, and cyclin D, which are related to cell cycle regulation and cell division control. Conclusion : OJEF is effective in regulating cell cycle of human melanoma cells and thus can be a good theraputic agent to treat patients with melanoma.

• International Journal of Oral Biology
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• 제43권2호
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• pp.61-68
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• 2018

Codium fragile (Suringar) Hariot is an edible green seaweed that belong to the Codiaceae family and has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria. Methanol extract of codium fragile has anti-oxidant, anti-inflammatory and anti-cancer properties, although the anti-cancer effect on oral cancer has not yet been reported. In this study, we investigated the anti-cancer activity and the mechanism of cell death by methanol extracts of Codium fragile (MeCF) on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that MeCF inhibits cell viability in a dose-dependent manner, and markedly induced apoptosis, as determined by the MTT assay, Live/Dead assay, and DAPI stain. In addition, MeCF induced the proteolytic cleavage of procaspase -3, -7, -9 and poly(ADP-ribose) polymerase(PARP), and upregulated or downregulated the expression of mitochondrial-apoptosis factor, Bax(pro-apoptotic factor), and Bcl-2(anti-apoptotic factor). Futhermore, MeCF induced a cell cycle arrest at the G1/S phase through suppressing the expression of the cell cycle cascade proteins, p21, CDK4, CyclinD1, and phospho-Rb. Taken together, these results indicated that MeCF inhibits cell growth, and this inhibition is mediated by caspase- and mitochondrial-dependent apoptotic pathways through cell cycle arrest at the G1/S phase in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, methanol extracts of Codium fragile can be provided as a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.