• 한국미생물·생명공학회지
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• 제29권3호
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• pp.181-185
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• 2001

유방암 세포주에서는 우수한 항암활성을 가진 것으로 알려진 indole-3-carbinol을 HepG2세포주에 시간과 농도별로 처리한 결과 cell growth inhibition을 확인하였으며, $IC_{50}$ 값은 48시간배양에서 $446\mu$M 72시간 배양에서 444$\mu$M로 나타났다. $400\mu$M의 I3C을 투여하고, 24, 48, 72시간에 HePG2 세포주의 cell cycle pattern을 분석한 결과, G1 phase에서 P21의증가와 함께 Cdk 6와 cyclin D의 확연한 감소와 Pb protein의 hypo-phosphorylation을 확인하였다. 반면 G2 phase에서는 I3C의 직접적인 억제로 인해 24시간 후부터 Cdc2와 cyclin B1가 급격히 감소하는것을 확인하였다. Flow cytomery 분석결과 I3C 처리 24시간 뒤 G2 arrest (25%)가 발생하였으며, 72시간이 지난후 G1 arrest (53%)가 발생하였다. 이러한 I3C의 간암세포주인 HePG2 cell의 cell cycle arrest가 apoptosis를 유발하는지를 알고자 caspase 3 Bcl2 Bax protein의 발현양상을 확인한 결과 아무런 변화가 보이지 않았다. 즉 I3C은 간암세포주인 HepG2 cell에서 apoptosis를 유도하지 못한다는것을 확인하였따. 결론적으로 I3C은 HepG2 세포주에서 G1와 G2 phase에서 cell cycle arrest는 발생시키나, 특이적으로 apoptosis 와는 연관되지 않는다는 사실을 확인하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.703-712
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• 2016

Monoclonal antibodies with specific antigens have been widely used as targeted therapy for cancer. Hep88 mAb is a monoclonal antibody which shows specific binding with anti-cancer effects against the HepG2 cell line. However, its mechanisms of action are still not completely understood. We examined cell cycling and apoptosis by flow cytometry and mRNA expression of factors involved in apoptosis and paraptosis in Hep88 mAb-treated HepG2 cells by real-time PCR. The cell-cycle analysis demonstrated that growth-inhibitory activity was associated with G2/M cell cycle arrest. Hep88 mAb induced a significant increase in apoptotic cell populations in a dose- and time-dependent manner. The mRNA expression results also suggested that the process triggered by Hep88 mAb involved up-regulation of tumor suppressor p53, pro-apoptotic Bax, Cathepsin B, Caspase-3 and Caspase-9, with a decrease of anti-apoptotic Bcl-2 - thus confirming paraptosis and apoptosis programmed cell death. These findings represent new insights into the molecular mechanisms underlying the anti-cancer properties of Hep88 mAb in liver cancer cells.

• 생명과학회지
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• 제21권11호
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• pp.1549-1557
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• 2011

TRAIL은 다양한 암세포에서 apoptosis를 유발하는 것으로 알려져 있으나 간암세포를 포함한 일부 암세포에서 TRAIL 저항성이 획득된 것으로 보고되어지고 있다. 대두의 대표적인 생리활성 물질인 isoflavonoid계열 genistein은 이미 많은 암세포에서 apoptotic 효능을 가진 것으로 알려져 있으나 TRAIL에 의한 apoptosis 유도에 미치는 영향과 기전에 대한 연구는 여전히 미비한 실정이다. 본 연구에서는 TRAIL 저항성을 가진 Hep3B 간암세포에서 TRAIL에 의한 apoptosis 유도를 genistein이 더욱 상승시킬 수 있음을 보고하고자 한다. 본 연구의 결과에 의하면, Hep3B 세포에 세포독성을 보이지 않는 범위의 genistein에 의한 TRAIL 유도 apoptosis 상승효과는 미토콘드리아의 기능 손상과 연관성이 있었다. 또한 genistein과 TRAIL 복합처리에 의한 apoptosis 유도는 p38 MAPK 활성 저하로 더욱 상승하였으며, 이는 Bid의 truncation 증가, pro-apoptotic 단백질인 Bax의 발현 증가와 anti-apoptotic Bcl-2의 발현 감소 및 미토콘드리아에서 세포질로의 cytochrome c 유출의 증가와 연관성이 있었다. 또한 p38 MAPK 억제제는 genistein 및 TRAIL 복합처리에 의한 caspase의 활성 증가와 PARP 단백질의 단편화를 촉진시켰으며, 이는 미토콘드리아의 기능적 손상 증가에 의한 것임을 알 수 있었다. 따라서 본 연구의 결과는 genistein이 TRAIL에 의한 apoptosis 유도를 효과적으로 증가시킬 수 있으며, 이러한 과정이 p38 MAPK 의존적으로 이루어짐을 알 수 있었다.

• Nutrition Research and Practice
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• 제7권3호
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• pp.153-159
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• 2013

We investigated whether the combination of phytochemicals and acetic acid in the form of fruit vinegar provides an additive effect on changes of mRNA levels related to fatty acid oxidation in human hepatocyte (HepG2). Among the seven fruit vinegars (Rubuscoreanus, Opuntia, blueberry, cherry, red ginseng, mulberry, and pomegranate) studied, treatment of HepG2 with pomegranate vinegar (PV) at concentrations containing 1 mM acetic acid showed the highest in vitro potentiating effect on the mRNA expression levels of peroxisome proliferator-activated receptor ${\alpha}$, carnitinepalmitoyl transferase-1, and acyl-CoA oxidase compared to the control group (P < 0.05). Reversed-phase liquid chromatography in combination with quadrupole time-of-flight mass spectrometry analysis revealed four potential compounds (punicalagin B, ellagic acid, and two unidentified compounds) responsible for altered gene expression in HepG2 cells treated with PV as compared with the others. Further investigations are warranted to determine if drinking PV beverages may help to maintain a healthy body weight in overweight subjects.

• Journal of Nutrition and Health
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• 제40권6호
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• pp.493-499
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• 2007

Celastrus orbiculatus (CO) has been used as a traditional herb medicine to treat fever, chill, joint pain, edema, rheumatoid arthritis and bacterial infection in China and Korea. In this study, we investigated anticarcinogenic effects of Celastrus orbiculatus (CO). CO was extracted with methanol (COM), and then further fractionated into four different types: methanol (COMM), hexane (COMH), butanol (COMB) and aqueous (COMA) partition layers. We determined the cytotoxicity of these four partitions in four kind of cancer cell lines, such as HepG2, MCF-7, HT29 and B16F10 Cells by MTT assay. Among various partition layers of CO, the COMM showed the strongest cytotoxic effects on cancer cell lines we used. We also observed quinone reductase (QR) induced effects in all partition layers of CO on HepG2 cells. The QR induced effects of COMM on HepG2 cells at 80 ${\mu}$ g/mL concentration indicated 3.28 to a control value of 1.0. The COMM showed the highest induction activity of quinone reductase on HepG2 cells among the other partition layers. Although further studies are needed, the present work suggests that CO may be a chemopreventive agent for the treatment of human cells.

• 동의생리병리학회지
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• 제22권2호
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• pp.377-384
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• 2008

The root of Vitis labrusca, is used as a source of health promoting drug in Korean traditional medicine. It has been reported that root of Vitis labrusca has antioxidant, anti lipid peroxidation and anti-reactive nitrogen species (RNS) activities. The aim of this study was to elucidate the molecular changes of apoptotic signaling pathways in phorbol 12-myristate 13 acetate (PMA)-induced human hepatocellular carcinoma cell line (Hep G2). The root of Vitis labrusca, ethanol extract (RVLEE) was tested for cell viability on Hep G2 cell using the MTT assay. RVLEE exhibited weak cytotoxic activity. However, treatment of Hep G2 cells with RVLEE suppressed PMA-induced cell proliferation. Also, dramatic changes of cell death signals in cellular molecules such as Chk2/Cds1, CIDE-B, CLIMP-63, Bax, Bcl-xL, C-myc, Bcl-2, Bric-5, NIP-3, TRAF2 and BAR but not CIDE-B and DR4. Futhermore, our results showed that the treatment of Hep G2 cells with 25 and $50\; {\mu}g/ml$ of RVLEE suppressed PMA-induced COX-2 gene activity. These data suggest that RVLEE have inhibitory effect of cell proliferation, induction of apoptosis and, thus, may offer therapeutic potential in Hep G2.

• 한국식품영양과학회지
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• 제34권3호
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• pp.323-329
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• 2005

인삼박의 가용성 추출물을 용출시킨 후 남은 잔여 묵인 인삼박에 상황버섯, 영지버섯, 운지버섯, 표고버섯 균사체를 접종ㆍ배양하여 얻어진 인삼박 균사체 추출액의 전자공여능 및 간암세포(Hep3B)와 고형암(S-180)의 증식에 미치는 영향을 조사하였다. 인삼박 균사체의 전자공여능은 500-10,000ppm 범위에서 농도가 진할수록 높게 나타났으며 운지가 4종류의 균사체 추출물 중 가장 높았다. 간암세포의 형태변화 및 증식 억 제 에 미 치 는 영 향은 에 탄을 추출물이 물 추출물보다 효과적이었으며, 60% 에탄을 추출물 5,000 ppm에서 상황, 영지,운지에 비해 표고가 99.1%로 가장 강한 세포증식억 제 효과를 나타내었다. S-180 고형 암 억제효과는 대조군에 비해 운지가 65%로 가장 컸으며 영지 61%, 표고 56%, 상황 59%의 고형암 억제효과를 나타내었다. 따라서 인삼박을 이용하여 배양된 버섯 균사체가 간암세포와 고형암의 증식 억제에 효과적인 것으로 관찰되므로써 항암물질의 자원으로서 그 활용성이 기대된다고 하겠다.

• 한국동물학회:학술대회논문집
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• 한국동물학회 1998년도 한국생물과학협회 학술발표대회
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• pp.360-360
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• 1998

C11, a chloride-containing VK3 analog, acts as a mediator of programmed cell death in SK-Hep-1 cell lines, but its molecular mechanisms linked to cell death are not understood. In this study, we investigated the expression of p21 gene and its relationship to apoptosis induced by C11. In SK -hep-1 cells, the addition of C11 resulted in time-dependent growth suppression and DNA fragmentation characteristics of apoptosis. p21 protein was induced during this process, while the protein level of p53 was not changed at the same condition. This apoptotic cell death with p21 induction was also observed in the Hep3B cells lacking functional p53 after treatment of C11. These results suggest that C11-induced apoptosis is associated with up-regulation of p21 protein in p53-independent pathway. Next, in order to confirm whether the p53-independent p21 induction is required for C11-induced apoptosis, we introduced the p21 gene into Hep3B. Overexpression of p21 did not affect the expression of the bcl-2 gene, but DNA fragmentation and PARa cleavage were significantly increased. These data indicate that p21 is involved in C11-induced apoptosis. Although Bcl-2 has been implicated to interfere with an essential signaling molecule involved in the apoptosis pathway, its molecular mechanism and target molecule are poorly understood. To determine the effects of bcl-2 overexpression on apoptosis and to investigate whether BcI-2 interfers with the p53-independent p21 pathway, we transfected the bcl-2 expression vector into SK - Hep-1 cels. Overexpression of Bcl-2 prevented C11-induced apoptosis. Taken together, C11-induced apoptosis is regulated by p52-independent p21 pathway and bcl-2 may inhibit functional activity of p21, therebe may inhibit the C11-induced apoptosis.ptosis.

• 한국환경성돌연변이발암원학회지
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• 제11권2호
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• pp.99-106
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• 1991

수용체를 통한 저밀도 지방단백질(LDL)의 세포내 이동과 함께 일어나는 지용성 돌연변이원인 벤조피렌의 세포내 이동에 관하여 조사하였다. [$^3$H]로 표지된 벤조피 렌의 Hep 2 세포내 이동을 조사한 결과, 배지에 LDL을 첨가한 경우. LDL이 첨가되지 않은 경우보다 3배나 많은 양의 벤조피렌이 세포내로 이동하여 세포내 물질과 결합하였음을 관찰하였다. 그러나 10$\mu$M의 황산구리로 LDL의 아포단백질을 변형 시킨 후 변형된 LDL을 배지에 첨가하고 벤조피렌의 세포내 이동을 조사한 건과, 정상 LDL이 첨가된 경우보다 벤조피렌의 세포내 이동이 현저히 감소하였다. 이 결과는 LDL을 이동체로 이용한 벤조피렌의 세포내 이동이 세포의 수용체와 LDL의 아포 단백질의 인식과정을 거친다는 사실을 뒷받침한다고 여겨진다.

• BMB Reports
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• 제46권10호
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• pp.513-518
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• 2013

We investigated the protective effects of Gymnaster koraiensis against oxidative stress-induced hepatic cell damage. We used two different cytotoxicity models, i.e., the administration of tert-butyl hydroperoxide (t-BHP) and acetaminophen, in HepG2 cells to evaluate the protective effects of G. koraiensis. The ethyl acetate (EA) fraction of G. koraiensis and its major compound, 3,5-di-O-caffeoylquinic acid (DCQA), exerted protective effects in the t-BHP-induced liver cytotoxicity model. The EA fraction and DCQA ameliorated t-BHP-induced reductions in GSH levels and exhibited free radical scavenging activity. The EA fraction and DCQA also significantly reduced t-BHP-induced DNA damage in HepG2 cells. Furthermore, the hexane fraction of G. koraiensis and its major compound, gymnasterkoreayne B (GKB), exerted strong hepatoprotection in the acetaminophen-induced cytotoxicity model. CYP 3A4 enzyme activity was strongly inhibited by the extract, hexane fraction, and GKB. The hexane fraction and GKB ameliorated acetaminophen-induced reductions in GSH levels and protected against cell death.