• Journal of Microbiology and Biotechnology
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• 제30권12호
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• pp.1885-1895
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• 2020

Rumex japonicus Houtt (RJH) is a valuable plant used in traditional medicine to treat several diseases, such as scabies and jaundice. In this study, Jurkat cell growth inhibitory extracts of R. japonicus roots were subjected to bioassay-guided fractionation, resulting in the isolation of three naphthalene derivatives (3-5) along with one anthraquinone (6) and two phenolic compounds (1 and 2). Among these compounds, 2-methoxystypandrone (5) exhibited potent anti-proliferative effects on Jurkat cells. Analysis by flow cytometry confirmed that 2-methoxystypandrone (5) could significantly reduce mitochondrial membrane potential and promote increased levels of mitochondrial reactive oxygen species (ROS), suggesting a strong mitochondrial depolarization effect. Real-time quantitative polymerase chain reaction (qPCR) analysis was also performed, and the results revealed that the accumulation of ROS was caused by reduced mRNA expression levels of heme oxygenase (HO-1), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, 2-methoxystypandrone (5) triggered strong apoptosis that was mediated by the arrest of the G0/G1 phase of the cell cycle. Furthermore, 2-methoxystypandrone (5) downregulated p-IκB-α, p-NF-κB p65, Bcl2, and Bcl-xl and upregulated BAX proteins. Taken together, these findings revealed that 2-methoxystypandrone (5) isolated from RJH could potentially serve as an early lead compound for leukemia treatment involving intracellular signaling by increasing mitochondrial ROS and exerting anti-proliferative effects.

• 동의생리병리학회지
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• 제21권1호
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• pp.204-208
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• 2007

Chaga mushroom extract is well known as immune modulator and anti-cancer agent. However, the molecular mechanism by which Chaga exerts cell cycle arrest and apoptosis of cancer cells is poorly understood. In this study, we demonstrated anti-proliferative effects of Chaga extract on murine melanoma B16 cells. Chaga extract dose-dependently inhibited cell growth along with the arrest of G0/G1 phase and the induction of apoptotic cell death. Treatment with Chaga extract resulted in a decrease of cyclin E, cyclin D1, cdk 2, cdk 4 expression levels. Furthermore, in vivo inoculation study of B16 melanoma cells into Balb/c mice Chaga extract markedly suppressed the metastatic growth of tumor cells (6 folds, p<0.05,). These results indicate that Chaga mushroom extract induces apoptosis of B16 melanoma cells through arrest of G0/G1 phase in cell cycle.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4655-4660
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• 2012

Opuntia humifusa, member of the Cactaceae family, was previously demonstrated to have radical scavenging, anti-inflammatory and anti-proliferative effects in in vitro models. It was suggested that O. humifusa could function in the prevention of carcinogenesis. To investigate the in vivo chemopreventive effect of O. humifusa, mice were fed a diet containing either 1% or 3% following 7, 12-dimethylbenz[a] anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) induction of skin carcinogenesis. Significant decrease in the numbers of papilloma and epidermal hyperplasia were observed in mice fed with O. humifusa, compared to the control group. O. humifusa also upregulated high total antioxidant capacity and level of phase II detoxifying enzyme such as superoxide dismutase and glutathione S-transferase activity in the skin. Lipid peroxidation activity level was measured in skin cytosol and significantly inhibited in 3% OH fed group compared to the control group. These results suggest that O. humifusa exerts chemopreventive effects on chemical carcinogenesis in mouse skin and that prevention effects are associated with reduction of oxidative stress via the modulation of cutaneous lipid peroxidation, enhancing of total antioxidant capacity especially in phase II detoxifying enzyme system and partial apoptotic influence.

• BMB Reports
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• 제46권12호
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• pp.611-616
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• 2013

Luteolin-7-O-glucoside (LUT7G), a flavone subclass of flavonoids, has been found to increase anti-oxidant and anti-inflammatory activity, as well as cytotoxic effects. However, the mechanism of how LUT7G induces apoptosis and regulates cell cycles remains poorly understood. In this study, we examined the effects of LUT7G on the growth inhibition of tumors, cell cycle arrest, induction of ROS generation, and the involved signaling pathway in human hepatocarcinoma HepG2 cells. The proliferation of HepG2 cells was decreased by LUT7G in a dose-dependent manner. The growth inhibition was due primarily to the G2/M phase arrest and ROS generation. Moreover, the phosphorylation of JNK was increased by LUT7G. These results suggest that the anti-proliferative effect of LUT7G on HepG2 is associated with G2/M phase cell cycle arrest by JNK activation.

• Biomolecules & Therapeutics
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• 제19권2호
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• pp.187-194
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• 2011

Atherosclerosis and post-angiography restenosis are associated with intimal thickening and concomitant vascular smooth muscle cell (VSMC) proliferation. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have anti-inflammatory and anti-tumor activities. The goal of the present study was to enhance the inhibitory effects of obovatol to improve its potential as a preventive or therapeutic agent in atherosclerosis and restenosis. Platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic smooth muscle cells (RASMCs) was examined in the presence or absence of a newly synthesized obovatol derivative, OD78. The observed anti-proliferative effect of OD78 was further investigated by cell counting and [$^3H$]-thymidine incorporation assays. Treatment with 1-4 ${\mu}M$ OD78 dose-dependently inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated RASMCs. Accordingly, OD78 blocked PDGF-BB-induced progression from the $G_0/G_1$ to S phase of the cell cycle in synchronized cells. OD78 decreased the expression levels of CDK4, cyclin E, and cyclin D1 proteins, as well as the phosphorylation of retinoblastoma protein and proliferating cell nuclear antigen; however, it did not change the CDK2 expression level. In addition, OD78 inhibited downregulation of the cyclin-dependent kinase inhibitor (CKI) $p27^{kip1}$. However, OD78 did not affect the CKI $p21^{cip1}$ or phosphorylation of early PDGF signaling pathway. These results suggest that OD78 may inhibit PDGF-BB-induced RASMC proliferation by perturbing cell cycle progression, potentially through $p27^{kip1}$ pathway activation. Consequently, OD78 may be developed as a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.

• 한국작물학회지
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• 제51권spc1호
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• pp.103-106
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• 2006

Anthocyanins are water-soluble glycosides and acylglycosides of anthocyanidins, having different color variations due to its substitution patterns. Anthocyanins, present in various fruits, vegetables and crops as natural colorant, have been well characterized for its bioactive properties, anti-oxidant, anti-cancer, anti-proliferative and anti-inflammatory properties. During extraction and purification, the factors, such as pH, temperature, oxygen, light, enzymes, nucleophilic agents, sugar derivatives and co-pigments, have affected on anthocyanin stability. For this reason, the extraction method should be thoroughly checked for the qualitative/quantitative analysis of anthocyanin in particular plant material. To identify the optimum extraction method of cyanidin-3-glucoside, major anthocyanin of dark purple-colored grains, Oryza sativa cv. Heugjinjubyeo, Phaselous vulgaris, Phynchosia gngularis, Sesamum indium, Rhynchosia nulubilis and Lablab purpureus, reversed-phase HPLC analysis using solvent system of acetonitrile, methanol and water were accomplished.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.122-122
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• 2003

Endometrial tissue is an interesting model for intrinsic and extrinsic factors, ie hormones and growth factors, involved in its normal pathologic development and its cyclic growth. The endometrial cells were isolated from endometrial tissue of the proliferative phase obtained by hysterectomy and separated stromal and epithelial cells.(omitted)

• 핵의학기술
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• 제13권3호
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• pp.43-47
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• 2009

$^{18}F$-FDG PET/CT는 암세포에서 당 대사가 항진되는 현상을 이용하여 암환자의 진단에 폭넓게 사용 되고 있으며, 악성 종양에 대부분 섭취 되는 것이 일반적이지만, 정상 조직에도 섭취되는 경우도 있다. 이러한 현상은 보통 소화기계에서 빈번히 일어나며, 월경을 하는 가임기 여성에게서 자궁 주위에서의 섭취가 일어나기도 한다. 특히 가임기 여성은 월경에서 각 주기 동안 난소는 월경기, 증식기, 배란기, 분비기 이렇게 4단계의 주기를 거친다. 이러한 월경 주기에 따른 $^{18}F$-FDG 섭취는 영상에 다양한 영향이 미치기 때문에, 본 연구는 자궁의 $^{18}F$-FDG 섭취와 월경주기와의 관계를 알아보고자 하였다. 2008년 1월부터 2009년 3월까지 부인과 질환이 없고 월경이 규칙적인 $38{\pm}7.93$세 여성 환자 200명을 대상으로 하였다. 검사 전 6~8시간 금식 후 $^{18}F$-FDG 370 MBq를 정맥주사하고, 1시간 동안 충분한 휴식 후 전신 PET/CT 검사를 시행하였다. 영상 분석은 CT 영상으로 난소와 자궁의 위치를 정확히 파악한 후 같은 위상의 영상에서 표준화섭취계수를 측정하여 분석하였다. 월경주기에 따라 SUV의 변화가 크지는 않았지만, 분명 차이가 있었으며, 월경기 $SUV_{max}$는 $3.17{\pm}1.59$, $SUV_{avg}$는 $2.89{\pm}1.04$였고, 증식기 $SUV_{max}$는 $2.98{\pm}1.14$, $SUV_{avg}$는 $2.40{\pm}0.88$였다. 그리고 배란기 $SUV_{max}$는 $3.71{\pm}1.67$, $SUV_{avg}$는 $3.59{\pm}1.76$였고, 분비기 $SUV_{max}$는 $3.1{\pm}1.80$, $SUV_{avg}$는 $2.58{\pm}1.39$였다. 가임기 여성은 월경 주기에 따라 자궁과 난소에서 일정한 주기로 변화가 일어나며, 이에 따라 $^{18}F$-FDG PET/CT에서도 변화가 일어난다. 월경기, 증식기, 배란기, 분비기 이렇게 4단계의 주기를 가지고 영상에서 변화가 일어나므로, 검사 전 가임기 여성의 월경 주기를 파악하여 검사 시에 활용한다면, 자궁주변의 병변의 진단에 큰 도움이 될 것으로 사료된다.

• 한국식품영양과학회지
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• 제40권6호
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• pp.767-774
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• 2011

본 연구는 간암세포주인 HepG2 cell line에서 녹차씨박 추출물을 에탄올, 석유 에테르, 에틸 아세테이트, 부탄올의 순으로 분획 및 열수 추출물을 조제하여 암세포 증식 억제능을 확인한 후 에탄올 추출물을 선정하여 항종양 및 항염증효과를 생화학적, 분자적 방법으로 분석하였다. 녹차씨박 에탄올 추출물(DGTSE)의 polyphenol 함량을 HPLC로 분석한 결과 EGC($1039.1{\pm}15.26\;{\mu}g/g$)> tannic acid($683.5{\pm}17.61\;{\mu}g/g$)> EC($62.4{\pm}5.00\;{\mu}g/g$)> ECG($24.4{\pm}7.81\;{\mu}g/g$)> EGCG($20.9{\pm}0.96\;{\mu}g/g$)> gallic acid($2.4{\pm}0.68\;{\mu}g/g$)의 순이었으나 caffeic acid는 검출되지 않았다. DGTSE의 농도가 $10\;{\mu}g$/mL 이상에서는 84.13%의 세포 증식 억제능($IC_{50}$: $6.58\;{\mu}g$/mL)을 보여 간암세포의 증식을 효과적으로 억제하였고 제1상효소계인 CYP1A1와 CYP1A2의 발현을 농도 의존적으로 감소시키는 것으로 나타났다. QR 활성은 DGTSE을 $20\;{\mu}g$/mL 농도로 처리 시 대조군에 비해 2.6배 증가하였으며 reporter gene activity로 측정한 ARE 활성은 1.94배로 각각 증가하였다. DGTSE의 처리는 염증생성 인자인 PGE2의 생성과 TNF-${\alpha}$의 단백질 발현은 유의적으로 저해하였으며 cytokine 반응, 염증, 세포성장조절과 같은 다양한 단계에 참여하는 전사인자인 NF${\kappa}$B의 핵으로의 translocation을 억제하였다. 이상의 결과에서 DGTSE은 간암세포인 HepG2 세포계에서 암세포 증식 억제능을 가지며 해독효소인 QR, ARE의 활성을 증진시키고 NF${\kappa}$B의 translocation을 방해하고 TNF-${\alpha}$의 단백질 발현과 $PGE_2$의 생성을 억제하여 암세포의 증식을 억제하였다. 따라서 녹차씨박 추출물에 함유된 암세포 증식효과를 나타내는 생리활성 물질들에 대한 연구가 앞으로 진행되어야 할 것으로 사료된다.

• 대한약침학회지
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• 제18권2호
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• pp.26-32
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• 2015

Objectives: Rheum undulatum L. has traditionally been used for the treatment of many diseases in Asia. However, its anti-proliferative activity in cancer has still not been studied. In the present study, we investigated the anti-cancer effects of methanol extract of Rheum undulatum L. (MERL) on human adenocarcinoma gastric cell lines (AGS). Methods: To investigate the anti-cancer effect of MERL on AGS cells, we treated the AGS cells with varying concentrations of MERL and performed 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Cell cycle analyses, measurements of the mitochondrial membrane potential (MMP), caspase activity assays and Western blots were conducted to determine whether AGS cell death occurred by apoptosis. Results: Treatment with MERL significantly inhibited growth of AGS cells in a concentration dependent manner. MERL treatment in AGS cells leaded to increased accumulation of apoptotic sub G1 phase cells in a concentration dependent manner. In control cultures, 5.38% of the cells were in the sub G1 phase. In MERL treated cells, however, this percentage was significantly increased (9.95% at $70{\mu}g/mL$, 15.94% at $140{\mu}g/mL$, 26.56% at $210{\mu}g/mL$ and 38.08% at $280{\mu}g/mL$). MERL treatment induced the decreased expression of pro-caspase-8 and -9 in a concentration dependent manner, whereas the expression of the active form of caspase-3 was increased. A subsequent Western blot analysis revealed increased cleaved levels of poly (ADP-ribose) polymerase (PARP) protein. Also, treatment with MERL increased the activities of caspase-3 and -9 compared with the control. MERL treatment increased the levels of the pro-apoptotic truncated Bid (tBid) and Bcl2 Antagonist X (Bax) proteins and decreased the levels of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein, whose is the stabilization of mitochondria. However, inhibitions of p38, extracellular signal regulated kinases (ERKs) and C-Jun N-terminal kinases (JNK) by MERL treatment did not affect cell death. Conclusion: These results suggest that MERL mediated cell death is associated with an intrinsic apoptotic pathway in AGS cells.