• 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.

• 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.

• 약학회지
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• 제55권1호
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• pp.49-55
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• 2011

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is one of the promising anti-cancer agent because of its ability to selectively induce apoptosis in tumor cell lines but not in normal cells. However, TRAIL resistance has been reported in some cancer cells including hepatocarcinoma cells. Therefore, studies of agents that sensitize TRAIL-resistant cancer cells could be a effective therapeutic approach in cancer management. In our study, we examined the effect of combination of TRAIL with apigenin in human hepatocellular carcinoma cells. As a result, the combined use of TRAIL and apigenin significantly enhanced the cytotoxicity in PLC-PRF5 cells. Flow cytometry analysis after annexin V-FITC/PI dual staining showed that this increase of cell cytotoxicity was related to enhanced apoptosis in combined treatment of TRAIL with apigenin. Furthermore, synergistic induction of apoptosis was also confirmed by observation of morphological changes and annexin V-FITC/PI fluorescence. Our findings suggests that apigenin has the potential to improve the efficiency of TRAIL-based therapies in human hepatocellular carcinoma cells. Further study is needed to reveal the molecular mechanisms of this combined therapy.

• 한국해양바이오학회지
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• 제14권2호
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• pp.93-101
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• 2022

Hizikia fusiforme, a type of brown algae, is widely used in Asian cuisine. It has been reported to have various pharmacological effects. In this study, the effects of the ethanol extract from H. fusiforme (EAHF) on the proliferation of human colon carcinoma cells were investigated. The effect on the survival of human hepatocarcinoma and colon carcinoma cells was examined, and results revealed that the anti-proliferative effects of EAHF were higher in colon carcinoma cells than in hepatocarcinoma cells. The inhibition of proliferation of HT29 colon carcinoma cells by EAHF treatment was closely related to the induction of apoptosis. EAHF treatment also increased caspase activity and poly(ADP-ribose) polymerase degradation, induced mitochondrial dysfunction, altered Bcl-2 family protein expression, and increased the rate of cytochrome c released from the mitochondria into the cytoplasm. Furthermore, the production of reactive oxygen species (ROS) was markedly stimulated by EAHF treatment, and when ROS production was blocked, EAHF-induced cytotoxicity was significantly attenuated. These results indicate that the anticancer activity of EAHF in HT29 colon carcinoma cells was induced by ROS-dependent mitochondrial impairment. While EAHF exhibited potent anticancer activity in colon carcinoma cells in this study, further studies on the active components of EAHF and their efficacy should be performed.

• 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.

• 한국식품영양과학회지
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• 제37권6호
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• pp.714-720
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• 2008

본 연구에서는 동충하초(C. militaris)의 항암작용 기전 해석을 위하여 Hep3B 간암세포의 apoptosis 유발에 미치는 동충하초 열수추출물(WECM)의 영향을 조사하였으며, apoptosis 조절에 중요한 몇 가지 유전자들의 발현 및 활성 변화를 조사하였다. AECM 처리에 의한 Hep3B 세포의 증식억제는 형태적 변형을 동반한 apoptosis 유도와 연관성이 있음을 DAPI 염색을 통한 apoptotic body 출현의 증가 및 flow cytometry 분석에 의한 sub-G1 기에 속하는 세포 빈도의 증가로 확인하였다. AECM 처리에 의한 apopotosis 유도에서 Bcl-2 family에 속하는 몇 가지 유전자들의 발현은 큰 변화가 없었으나, caspase-3 및 -8의 활성이 매우 높게 증가 되었으며 이는 PARP 및 ${\beta}$-catenin 단백질의 분해와 연관성이 있었다. 또한 caspase-3 선택적 저해제인 z-DEVD-fmk로 caspase-3의 활성을 인위적으로 차단시켰을 경우, AECM에 의한 apoptois 유도 현상이 유의적으로 감소되어 AECM에 의한 Hep3B 세포의 apoptosis 유발에 caspase-3이 중요한 역할을 하고 있음을 알 수 있었다. 본 연구의 결과만으로 동충하초에 의한 간암세포의 증식억제 기전을 명확하게 제시할 수는 없으나, 이상의 결과들은 동충하초의 생화학적 항암기전 해석을 이해하는데 중요한 기초자료로서 활용될 수 있을 것으로 생각된다.

• 한국동물학회:학술대회논문집
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• 한국동물학회 1998년도 한국생물과학협회 학술발표대회
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• pp.316.1-316
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• 1998

No Abstract, See Full Text

• 한국동물학회:학술대회논문집
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• 한국동물학회 1998년도 한국생물과학협회 학술발표대회
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• pp.315.2-315
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• 1998

No Abstract, See Full Text

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2007년도 제48회 학술심포지움 및 추계국제학술대회
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• pp.34.1-34.1
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• 2007

See Full Text

• Journal of Microbiology and Biotechnology
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• 제18권3호
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• pp.512-519
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• 2008

Three different polysaccharide-peptide complexes (PPC, named as Fr-I, Fr-II, and Fr-III) were produced by submerged mycelial culture of an entomopathogenic fungus Cordyceps sphecocephala, and their anticancer activities were investigated in human hepatocarcinoma (HepG2) and neuroblastoma (SK-N-SH) cells. The highest inhibitory effects of PPC on both HepG2 and SK-N-SH cells were achieved with Fr-I, whereas Fr-III with low molecular mass showed lower inhibition effects. Interestingly, the inhibitory effects of the three fractions were increased after protease digestion, suggesting that the inhibitory effects resulted mainly from the carbohydrate moiety, at least in the case of Fr-II and Fr-III, of PPC. The results of DNA fragmentation in PPC-induced apoptotic cells were confirmed by both DNA ladder assay and comet assay. Our investigation also showed that PPC-induced apoptosis of both cancer cells was associated with intracellular events including DNA fragmentation, activation of caspase-3, and modulation of Bcl-2 and Bax. We conclude that PPC has potential as a novel therapeutic agent for the treatment of both HepG2 and SK-N-SH cancer cells without any cytotoxicity against normal cells.