• Toxicological Research
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• 제12권2호
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• pp.271-275
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• 1996

Carcinogenic potential of HPV-16 DNA and NNK in a human keratinocyte cell line was assessed to study effects of viral-chemical interaction. Human cells were transfected with HPV-16 DNA and 6 clonal cell lines were subsequently obtained. Clonal line-3 and 6 at passage 7 showed characteristics of tumor cells such as increases of saturation density, soft-agar colony formation, cell aggregation and foci appearance. Among cells treated with 1$\mu M$, 10$\mu M$, 100$\mu M$ or 1 mM of NNK for 4 weeks, 100$\mu M$ treatment showed most tumorigenic characteristics at passage 7. These results indicate that either HPV-16 or NNK alone is tumorigenic in this in human in vitro model. When cells transfected with HPV-16 were subsequently exposed by 100 uM NNK for 4 weeks, all the clonal cells except clone-1 showed higher levels of tumor cell characteristics than HPV-16 DNA or NNK exposure alone. Clonal line-6, the most tumorigenic cells, showed higher transcriptional level of fibronectin and lower level of TGF-$\beta_1$, as compared to control cells, suggesting that alteration of growth factor or extracellular matrix may play a role in carcinogenesis process induced by HPV-16 and NNK. Taken together, the present study indicates that viral-chemical interactions between HPV-16 DNA and NNK enhance carcinogenic potentials of human cells and implies that smoking among people infected with human papillomavirus may pose an additional risk of causing cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2883-2888
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• 2014

Background: Realgar which contains arsenic components has been used in traditional Chinese medicine (TCM) as an anticancer drug. However, neither Realgar nor its formula are soluble in water. As a result, high dose of Realgar has to be administered to achieve an effective blood medicine concentration, and this is associated with adverse side effects. The objective of the present study was to increase the solubility of a formula using hydrometallurgy technology as well as investigating its effects on in vitro and in vivo cell proliferation and apoptosis in Sarcoma-180 cell line. Materials and Methods: Antiproliferative activity of Realgar Bioleaching Solution (RBS) was evaluated by MTT assay. Further, effects of RBS on cell proliferation and apoptosis were studied using flow cytometry and transmission electron microscopy. Kunming mice were administered RBS in vivo, where arsenic specifically targeted solid tumors. Results: The results indicated that RBS extract potently inhibited the tumor growth of Sarcoma-180 cell line in a dose-dependent manner. Flow cytometry and transmission electron microscopy further indicated that RBS significantly induced cell apoptosis through the inhibition of cell cycle pathway in a dose-dependent manner. Further, on RBS administration to mice, arsenic was specifically targeted to solid tumor.s Conclusions: RBS could substitute for traditional Realgar or its formula to work as a potent tool in cancer treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2655-2661
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• 2014

Background: Talin-1 is a cytoskeleton protein that participates in cell migration and plays a role in tumor formation, migration, and metastasis in different types of cancer. Chinese investigators have observed that the levels of Talin-1 protein and mRNA expression in HCC tissues are significantly lower than in the adjacent non-cancerous tissue. However, Japanese investigators have reported that Talin-1 is upregulated in HCC. Tln2 as homologous gene of Tln-1, which encodes a very similar protein, but the role of Talin-2 is very little known in primary liver cancer (PLC). We investigated whether the expression of Talin-1 in PLC may be associated with the histological subtype as well as the role of Talin-1 in tumor cell invasion and migration using human hepatocellular carcinoma cell lines. Materials and Methods: We measured the mRNA expression levels of Talin-1 and Talin-2 in five human liver cancer cell lines and normal human liver cell ($LO_2$ cell line) by real-time PCR and the protein expression levels of Talin-1 by Western blot. Migration and invasion of the cells were assessed using transwell assays and cell scratch experiments, respectively, and proliferation was assessed by soft AGAR colony formation. Results: Talin-1 and Talin-2 expression differed significantly between the five human liver cancer cell lines and $LO_2$ cell line (p<0.05). Compared with the $LO_2$ cell line, the invasion and migration capabilities of the five cancer cell lines differed significantly (p<0.05). Similarly, the colony-forming ability differed (p<0.05). Conclusions: High levels of Talin-1 expression are correlated with reduced invasion and migration as well as decreased malignancy in human liver cancer cell lines; the suppression of Talin-1 promotes invasion and migration. In addition, Talin-2 may be correlated with invasion and migration in human hepatocellular carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2447-2451
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• 2013

Objective: To study changes of tumor associated carbohydrate antigen (TACAs) expression and mRNA levels for tumor associated glycosyltransferases, and assess subcellular localizations of N-acetyl galactosyltransferases (GalNAc-Ts) in the K562 leukemia cell line after imatinib treatment. Methods: RT-PCR was performed to analyze the expression of glycosyltransferases which synthesize O-glycan in tumor-associated carbohydrate antigens (TCTAs). The expression of Tn antigen, T antigen and sialyl T antigen on K562 cell membranes was measured by flow cytometry after treatment with different concentrations of imatinib. Co-localization of GalNAc-Ts and ER (endoplasmic reticulum) was determined by confocal laser scanning microcopy. Results: Transcript expression levels of several glycosyltransferases related to TCTAs were decreased after imatinib ($0-0.3{\mu}M$) treatment. Expression of Tn antigen and T antigen was increased while that of sialyl T antigen was decreased. Co-localization of GalNAc-Ts and ER was reduced by $0.2{\mu}M$ of imatinib. Conclusion: Imatinib inhibited the expression of O-glycan related TACAs and several related glycosyltransferases, while decreasing the co-localization of GalNAc-Ts and ER and normalizing O-glycosylation in the K562 human leukemia cell.

• BMB Reports
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• 제45권9호
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• pp.526-531
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• 2012

Many malignant tumors become resistant to tumor necrosis factor-alpha (TNF-${\alpha}$)-induced cell death during carcinogenesis. In the present study, we examined whether parkin acts as a tumor suppressor in HeLa cells, a human cervical cancer cell line resistant to TNF-${\alpha}$-induced cell death. TNF-${\alpha}$-treatment alone did not affect HeLa cell viability. However, expression of parkin restored TNF-${\alpha}$-induced apoptosis in HeLa cells. Increased cell death was due to the activation of the apoptotic pathway. Expression of parkin in TNF-${\alpha}$-treated HeLa cells stimulated cleavage of the pro-apoptotic proteins caspase-8, -9, -3, -7 and poly ADP ribose polymerase (PARP). In addition, parkin expression resulted in decreased expression of the caspase inhibitory protein, survivin. These results suggest that parkin acts as a tumor suppressor in human cervical cancer cells by modulating survivin expression and caspase activity. We propose that this pathway is a novel molecular mechanism by which parkin functions as a tumor suppressor.

• Journal of Photoscience
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• 제9권3호
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• pp.41-43
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• 2002

PDT-mediated cyototoxicity basically depends on the penetrated light-dose into the tumor tissue. This limits the efficiency of PDT to the superficial tumor region typically less than 1 cm. The localized photochemical generation of reactive oxygen species, including singlet oxygen is known to increase expression of assortment of early response genes including heat shock protein. In order to increase PDT cytotoxicity in the treatment of solid tumor, it is desirable to combine PDT with other therapeutic effects. In this preliminary study we evaluated enhanced cytotoxicity from the PDT-mediated expression of thymidine kinase in a transfected tumor cell line. Two types of photo sensitizers, a hematoporphyrin derivative(Photogem, Russia) and aluminium sulphonated phthalocyanine(Photosense, Russia) were used to evaluate the overexpression of hsp-70 in PDT-treated cell. Transient increase of hsp-70 was observed at 6-8 hrs later following irradiation in the photosense-treated cell whereas it was not observed in Photogem-treated cell. In the presence of ganciclovia, transfected cell showed a 17％ increase in the cytotoxicity compared to the PDT only cell.

• BMB Reports
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• 제40권2호
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• pp.290-294
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• 2007

Saxatilin is a disintegrin known to inhibit tumor progression in vivo and in vitro. The role of saxatilin in cancer cell invasion was examined by a modified Boyden chamber assay in MDAH 2774 human ovarian cancer cell line. Saxatilin (50 nM) significantly inhibited cancer cell invasion induced by tumor necrosis factor-$\alpha$ (TNF-a$\alpha$). Saxatilin also reduced MMP-9 mRNA levels in cancer cells in a dosedependent manner. In addition, TNF-$\alpha$-induced MMP-9 activity was reduced by the treatment of saxatilin. These results indicate that transcriptional regulation of MMP-9 is an important mechanism for the tumor suppressive effects of saxatilin in MDAH 2774 human ovarian cancer cells.

• Tuberculosis and Respiratory Diseases
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• 제44권6호
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• pp.1271-1284
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• 1997

연구배경 : 종양괴사인자(tumor necrosis factor ; TNF)는 다양한 생물학적 기능을 가지고 있는 바, 그 중 생체 외에서 증명된 뚜렷한 항암 효과로 말미암아 최근 항암 유전자요법의 중요한 대상으로 관심을 모으고 있다. 현재 유전자 이입의 기술적 문제로 생체 외에서 암세포에 유전자 이입을 시행한 후 이를 다시 환자의 생체내로 이식하는 방법이 연구의 주종을 이루고 있다. 그러나 저자들의 과거의 연구를 포함한 여러 연구에서 TNF가 이입된 암세포는 TNF에 대해 내성을 보이는 것으로 증명되었고 이에는 새로이 방어 단백질을 합성하는 것이 관여할 것이라는 시사가 있었다. 이 획득내성의 기전을 밝히는 것이 종양생물학의 이해를 넓히고 보다 효과적인 항암 유전자요법을 개발하기위한 매우 중요한 과제로 생각된다.

• Journal of Nutrition and Health
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• 제35권2호
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• pp.201-206
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• 2002

This study was designed to research the anti-tumor effect of omija (methanol extract(I), malic acid & ethanol extract(II), and water extract (III)) on human liver cancer cell line SNU-398. MTT assay was used in vitro. The longer th\ulcorner exposure time and the higher the concentration of Omija extract, the stronger the anti-tumor effect. When the concentration of (II) was 1,600 $\mu\textrm{g}$/$m\ell$ and the exposure time reached 96 hours, The strongest propagation inhibition effect occurred with the viability rate as low as 5.06%. $IC_{50}$/ value was 363 $\mu\textrm{g}$/$m\ell$. Under the condition of 1,600$\mu\textrm{g}$/$m\ell$ and 96 hours, (I) lowered the rate to 7.75%. $IC_{50}$/ value was 489 $\mu\textrm{g}$/$m\ell$. When it was 1,600$\mu\textrm{g}$/$m\ell$ and 72 hours, (III) the rate decreased to 15.97%. $IC_{50}$/ value was 703 $\mu\textrm{g}$/$m\ell$. In all three cases, the viability of the cancer cell decreased significantly when the exposure time ranged between 24 and 48 hours.

• 한국미생물·생명공학회지
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• 제21권4호
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• pp.316-321
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• 1993

MCH-201 was isolated from the mycelium of Streptomyces sp. Ba16 as a potent effector on proliferation and morphology of human breast tumor cell line, MCF-7. Morphological change could be observed at concentration between 2.5${\mu}$g/ml and 250pg/ml and showed cytotoxic effect at the concentration of more than 5${\mu}$g/ml. This compound also showed inhibitory effect on DNA synthesis of hepatoma cells, Hepa 1c1c7, and strong cytotoxic effect on proliferation of human tumor cell lines, A549 and XF498.