• 제목/요약/키워드: Hepatocarcinoma

검색결과 80건 처리시간 0.065초

In Vivo Anti-tumor Activity of 3-Methyl-6-allylthiopyridazine in Nude Mice Xenografted with Hep-G2 Hepatocarcinoma

  • Kwon, Soon-Kyoung;Moon, Aree
    • Biomolecules & Therapeutics
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    • 제13권2호
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    • pp.113-117
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    • 2005
  • Organosulfur compounds have been shown to exert an anti-cancer activity. In an attempt to develop novel chemopreventive and anti-cancer agents for liver cancer, we synthesized allylthiopyridazine derivatives. We have previously shown that allylthiopyridazine derivatives exert inhibitory effects on proliferation, invasion and migration of SK-Hep-1 hepatocarcinoma cells in vitro. The in vivo anti-tumor effect of 3-methvl-6-allylthiopy-ridazine, named as K6, was also reported. In this study, we further investigated the preclinical anti-cancer efficacy of K6 for hepatocarcinoma using nude mice xenografted with Hep-G2 hepatocellular carcinoma cells. K6(20-100 mg/kg, orally administered everyday for 30 days) markedly decreased the tumor volume of Hep-G2 cell-transplanted nude mice as evidenced by ultrasonographic and plethysmogranhic analyses. The inhibitory effect on tumor volume was lower than that exerted by doxorubicin (2 mg/kg), intravenously injected) which was used as a positive control. This study shows that K6 efficiently suppresses xenograft tumor growth, revealing K6 as apotential anti-cancer agent for suppressing in vivo progression of liver cancer. Given that hepatocarcinoma is among the most prevalent and lethal malignancies and there is no effective treatment to date, our study may contribute to the potential drug development for liver cancer.

Identification of matrix metalloproteinases secreted by human hepatocarcinoma HepG2 cells

  • Lee, Young Jae;Kim, Keun Cheon;Lim, Jeong Mook;Lee, Seung Tae
    • 한국동물생명공학회지
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    • 제37권1호
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    • pp.62-66
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    • 2022
  • To date, the development of anticancer drugs has been conducted using two-dimensional (2D) cell culture systems. However, since cancer cells in the body are generated and developed in three-dimensional (3D) microenvironments, the use of 2D anticancer drug screening can make it difficult to accurately evaluate the anticancer effects of drug candidates. Therefore, as a step towards developing a cancer cell-friendly 3D microenvironment based on a combination of vinylsulfone-functionalized polyethylene glycol (PEG-VS) with dicysteine-containing crosslinker peptides with an intervening matrix metalloproteinase (MMP)-specific cleavage site, the types of MMPs secreted from human hepatocarcinoma HepG2 cells, a representative cancer cell, were analyzed transcriptionally and translationally. MMP3 was confirmed to be the most highly expressed protease secreted by HepG2 cells. This knowledge will be important in the design of a crosslinker necessary for the construction of PEG-based hydrogels customized for the 3D culture of HepG2 cells.

Chemopreventive Allylthiopyridazines, K compounds, Inhibit Invasion, Migration and Angiogenesis in SK-Hep-1 Hepatocarcinoma Cells Possibly via MMP-2 Downregulation

  • Lee, Eun-Jung;Shin, Ilc-Hung;Kwon, Soon-Kyung
    • 대한약학회:학술대회논문집
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    • 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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    • pp.218.1-218.1
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    • 2003
  • Dietary organosulfur compounds have been shown to inhibit the proliferation of tumor cells. Synthetic sulfur-containing compounds including oltipraz exert chemopreventive and hepatoprotective effects. We previously showed that synthetic allylthiopyridazine derivatives designated as K compounds induced apoptosis in SK-Hep-1 hepatocarcinoma cells (Eur. J. Cancer: 37, 2104-10, 2001). (omitted)

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Expression of IER3 in Primary Hepatocarcinoma: Correlation with Clinicopathological Parameters

  • Liu, Zhong;Wang, Xin-Mei;Jia, Tong-Fu;Zhai, Yi;Sun, Ling-Yan;Cheng, Yu-Ping;Zhang, Yue-Min;Liu, Shi-Hai;Liang, Jun
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권2호
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    • pp.679-682
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    • 2015
  • Background: Studies indicate the immediate early response gene 3 (IER3) is involved in many biological processes. Recently, it was discovered that IER3 plays an important role in tumorigenesis and tumor progression. Thus it may be a valuable biomarker in tumor. This study was designed to investigate the expression status of IER3 in primary hepatocarcinoma (PHC) and correlation with clinicopathological parameters. Materials and Methods: Real-time PCR was performed to evaluate the expression levels of IER3 in 62 pathologically diagnosed human PHC specimens. Results: A statistically significant association was disclosed between the expression of IER3 and P53 mutant protein (short for P53), Ki-67, EGFR and the biggest diameter, differentiation grade of tumor. Conclusions: This work is the first to shed light on the potential clinical usefulness of IER3, as an efficient tumor biomarker in PHC.

Korean Mistletoe Lectin-induced Apoptosis in Hepatocarcinoma Cells is Associated with Inhibition of Telomerase via Mitochondrial Controlled Pathway Independent of p53

  • Park, Won-Bong;Lyu, Su-Yun;Choi, Sang-Ho
    • Archives of Pharmacal Research
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    • 제25권1호
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    • pp.93-101
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    • 2002
  • The extract of European mistletoe ( Viscum album, L) has been used in adjuvant chemotherapy of cancer and mistletoe lectins are considered to be major active components. The present work was performed to investigate the effects of Korean mistletoe lectin (Viscum album L. coleratum agglutinin, VCA) on proliferation and apoptosis of human hepatoma cells as well as the underlying mechamisns for these effects. We showed that VCA induced atoptosis in both SK-Hep-1 and Hep 3B (p53-negative) cells through p53- and p21 -independent pathways. VCA induced apoptosis by down-regulation of Bcl-2 and by up-regulation of Bax functioning upstream of caspase-3 in both cell lines. In addition, we observed down-regulation of telomerase activity in both VCA-treated cells. Our results provide direct evidence of the anti-tumor potential of this biological response which comes from inhibition of telomerase and consequent inducing apoptosis. VCA-induced apoptosis is regulated by mitochondria controlled pathway independently of p53. These findings are important for the therapy with preparation of mistletoe because they show that telomerase-dependent mechanism can be targeted by VCA in human hepatocarcinoma. Taken together, our results suggest that the VCA, considered as a telomerase-inhibitor, can be envisaged as a candidate for enhancing sensitivity of conventional anticancer drugs.

Synthesis of 3-Alkylthio-6-Allylthiopyridazine Derivatives and Their Antihepatocarcinoma Activity

  • Kwon Soon-Kyoung;Moon Aree
    • Archives of Pharmacal Research
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    • 제28권4호
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    • pp.391-394
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    • 2005
  • The allylthio group of allicin and other organosulfur compounds, isolated from garlic, is considered a pharmacophore, and a key structure component of the molecule, which affords biological activities. In the foregoing studies, various 3-alkoxy-6-allylthiopyridazine derivatives (K­compounds) were synthesized, and their biological activities tested in animals. As expected, the various derivatives showed good hepatoprotective activities on carbon tetrachloride-treated mice and aflatoxin B1-treated rats, and chemopreventive activities on hepatocarcinoma cells in rats. Other new pyridazine derivatives, with the oxygen atom at the 3-position of the 3-alkoxy­6-allylthiopyridazine displaced by sulfur (S), were synthesized, and their activities tested in vitro. Thio-K6, one of the sulfur-substituted compounds, showed better chemopreventive activity toward hepatocarcinoma cells.

Viscum Album Var Hot Water Extract Mediates Anti-cancer Effects through G1 Phase Cell Cycle Arrest in SK-Hep1 Human Hepatocarcinoma cells

  • Cruz, Joseph Flores dela;Kim, Yeon Soo;Lumbera, Wenchie Marie Lara;Hwang, Seong Gu
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권15호
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    • pp.6417-6421
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    • 2015
  • Viscum album var (VAV) also known as mistletoe, has long been categorized as a traditional herbal medicine in Asia. In addition to its immunomodulating activities, mistletoe has also been used in the treatment of chronic hepatic disorders in China and Korea. There are numerous reports showing that VAV possesses anti-cancer effects, however influence on human hepatocarcinoma has never been elucidated. In the present study, hot water extracts of VAV was evaluated for its potential anti-cancer effect in vitro. SK-Hep1 cells were treated with VAV (50-400ug/ml) for both 24 and 48 hours then cell viability was measured by cell counting kit-8 (CCK-8). Flow cytometry analysis was used to measure the proportion of SK-Hep1 in the different stages of cell cycle. RT-PCR and Western blot analysis were conducted to measure expression of cell cycle arrest related genes and proteins respectively. VAV dose dependently inhibited the proliferation of SK-Hep1 cells without any cytotoxicity with normal Chang liver cell (CCL-13). Flow cytometry analysis showed that VAV extract inhibited the cell cycle of SK-Hep1 cells via G1 phase arrest. RT-PCR and Western blot analysis both revealed that cyclin dependent kinase 2 (Cdk2) and cyclin D1 gene expression were significantly down regulated while p21 was upregulated dose dependently by VAV treatment. Combined down regulation of Cdk2, Cyclin D1 and up regulation of p21 can result in cell death. These results indicate that VAV showed evidence of anti-cancer activity through G1 phase cell cycle arrest in SK-Hep1 cells.

Preventive Effect of Hydrazinocurcumin on Carcinogenesis of Diethylnitrosamine-induced Hepatocarcinoma in Male SD Rats

  • Zhao, Ji-An;Peng, Li;Geng, Cui-Zhi;Liu, Yue-Ping;Wang, Xu;Yang, Hui-Chai;Wang, Shi-Jie
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권5호
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    • pp.2115-2121
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    • 2014
  • The purpose of the present study was to evaluate the preventive effects of hydrazinocurcumin (HZC) on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in a male Sprague Dawley (SD) rat model. One hundred and twenty male SD rats used in this study were divided into six groups. Those receiving DEN with curcumin (CUR) or HZC were studied compared with the DEN-alone group. The study demonstrated that DEN induced severe histological and immunohistochemical changes in liver tissues, significantly increasing the levels of liver marker enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), ${\gamma}$-glutamyltransferase (GGT) and total bilirubin level (TBL)). The hepatocarcinoma incidences were 100.0%, 36.7% and 20.0% in the DEN-alone, DEN-CUR and DEN-HZC groups, respectively. Although macroscopic and microscopic features suggested that both CUR and HZC were effective in inhibiting DEN-induced hepatocarcinogenesis, HZC was exerted a stronger influence. Immunohistochemical analysis with PCNA demonstrated significantly differences among the groups (all P < 0.05). Taken together, the results suggested application of CUR and HZC could prevent the occurrence of carcinogenesis and HZC may be a more potent compound for prevention of DEN-induced hepatocarcinogenesis in rats than CUR.

산겨릅나무 추출물의 간암세포의 증식억제 효과 (Effect of Acer tegmentosum M. Extracts on Hepatocarcinoma Cell)

  • 권하나;방우석;김주영;박정륭;전정례
    • 한국식품과학회지
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    • 제43권6호
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    • pp.787-790
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    • 2011
  • 본 연구는 간암세포 HepG2의 증식을 억제하고 세포 사멸을 유도하는 천연소재 발굴을 목적으로, 산겨릅나무 분획 추출물을 이용하여 간암세포 HepG2의 증식에 미치는 영향을 확인하였다. 간암세포의 생존율에 분획별 추출물이 미치는 영향을 알아보기 위하여 분획물을 24시간, 48시간 동안 농도별로 처리하여 살아있는 세포를 계수한 결과 24시간 처리 시 모든 분획에서 농도 의존적으로 유의하게 생존율이 감소하였으며 유기용매 분획물들이 수용성 용매 추출물보다 높은 생육 억제 활성을 보였다. 48시간 처리 시에도 같은 경향이 나타났으며 24시간에 비하여 세포 생존율이 비슷하거나 조금 더 감소하였다. MTT assay를 통한 세포 생존 억제율의 측정 결과 BuOH 분획물은 간암세포에 대해 농도 의존적으로 생존 억제율을 증가시켰다. 형광현미경을 이용한 세포형태 관찰에서는 BuOH 분획물의 농도 의존적으로 세포의 형태가 응축되고 무정형으로 세포사멸이 나타나 apoptotic cell의 전형적인 양상을 확인할 수 있었다. Hong 등(10)의 연구에서 산겨릅나무의 추출물 중 ethyl acetat와 butanol 분획에서 뛰어난 항산화성과 항지질과산화 활성이 있음을 밝힌 내용과 Shin 등(11)의 위암, 간암, 폐암 및 유방암 세포 등에서 암세포 생육억제효과의 보고와도 유사한 경향이 나타남을 알 수 있었다. 이상의 실험을 통해 산겨릅나무가 간암세포의 성장을 저해하는 효과가 있음을 확인할 수 있었으며 앞으로 식용 및 약용자원으로서 활용가능성이 높은 것으로 판단된다.