• Journal of Oral Medicine and Pain
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• v.36 no.1
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• pp.11-20
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• 2011

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent. And it is known that antitmor activity of VPA is associated with its targeted at histone deacetylases. 17AAG, Inhibition of HSP90 leads to the proteasome degradation of the HSP90 client proteins, such as Akt, Raf/Ras, Erk, VEGF, cyclin D and p53, and causes potent antitumor activity. It is reported that 17AAG-induced HSP90 inhibition results in prevention of cell proliferation and induction of apoptosis in several types of cancer. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and the HSP90 inhibitor, 17AAG on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and 17AAG showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-3, caspase-7 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or 0.5 ${\mu}M$ 17AAG for 48 h did not induce apoptosis, the co-treatment with them induced prominently apoptosis. Therefore our data in this study provide the possibility that combination therapy with VPA and 17AAG could be considered as a novel therapeutic strategy for human osteosarcoma.

• Korean Journal of Medicinal Crop Science
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• v.10 no.2
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• pp.132-138
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• 2002

This study was performed to determine the antimutagenic and cytotoxic effect of ,Kalopanacis cortex endothelium. Methanol extract was used on Salmonella typhimurium TA98, TA100 and three cancer cell lines. In the Ames test, methanol extract of Kalopanacis cortex endothelium alone did not exhibit any mutagenicity but showed substantial inhibitory effects against mutation induced by 4-nitroquinoline-l-oxide(4NQO), N'-methyl- N'-nitro-N-nitrosoguanidine(MNNG) and benzo(a)pyrene(B(a)P). The methanol extract of Kalopanacis cortex endothelium showed approximately 79.29% and 75.38% inhibitory effect on the mutagenesis induced by 4NQO and B(a)P, respectively, against TA98 strain. Whereas 79.49%, 89.3% and 68.85% inhibitions were observed on the mutagenesis induced by 4NQO, MNNG and B(a)P against TA100 strain. Methanol extracts from Kalopanacis cortex endothelium showed high antimutagenic effects against 4NQO, MNNG and B(a)P. The anticancer effects of methanol extract from Kalopanacis cortex endothelium against human lung carcinoma(A549), human breast adenocarcinoma (MCF-7) and human hepatocellular carcinoma(Hep3B) were investigated. The treatment of 0.5mg/ml Kalopanacis cortex endothelium methanol extracts had the highest cytotoxicity against A549(81.54%), followed by MCF-7(81.92%) and Hep3B (78.57%). In contrast 0.5mg/ml treatment of methanol extracts from Kalopanacis cortex endothelium had only $4{\sim}25%$ cytotoxicity on normal human liver cell(293).

• Food Science and Preservation
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• v.11 no.4
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• pp.550-556
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• 2004

In the present study, we investigated the antimutagenic and cytotoxic effects of Acer ginnala Max. bark extract on S. typhimurium TA98, TA100 and cancer cell lines with Ames test and SRB assay, respectively. They were extracted with methanol and then fractionated using hexane, chloroform, ethyl acetate, butanol, and water to obtain the fractions. The inhibition rate of methanol ($200\;{\mu}g/plate$) of Acer ginnala Max. bark extract in the Salmonella typhimurium TA100 strain showed $83.3\%$ against the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In addition, the suppression of methanol extract with same concentration of in the Salmonella typhimurium TA98 and TA100 strains showed $80.3\%\;and\;92.7\%$ inhibition against 3-amino-1,4-dimethyl-5H-pyrido-(4,3-b)indol (Trp-P-1), respectively. The cytotoxicity effects of Acer ginnala Max. bark extract against the cell lines with human lung carcinoma (A549), human gastric carcinoma (AGS), human hepatocellular carcinoma (Hep3B) and human breast adenocarcinoma (MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL Acer ginnala Max. bark methanol extract of methanol showed strong cytotoxicities of $77.3\%,\;90.4\%,\;88.9\%,\;and\;83.7\%$ against A549, AGS, Hep3B and MCF-7, respectively.

• Journal of Life Science
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• v.18 no.1
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• pp.16-22
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• 2008

In this study to evaluate the involvement of EGFR, HER-2/neu and ALCAM (CD166) oncogene products in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 49 mammary tumors were analyzed immunohistochemically using antibodies against human EGFR and HER-2/neu and ALCAM. These 49 tumors were divided into 2 groups: 22 benign (19 adenoma, 3 benign mixed tumors) and 27 malignant tumors (2 simple adenocarcinomas, 5 complex adenocarcinomas, 3 solid carcinoma, 5 sclerosing carcinoma, 8 malignant mixed tumors and 4 malignant myoepithelioma). As a result of immunostaining, 31.8% (7/22) of the benign tumors and 29.6% (8/27) of the malignant tumors expressed the HER-2/neu oncogene product, EGFR expression was detected in 27.3% (6/22) of benign tumors and in 22.2% (6/27) of the malignant tumors. ALCAM expression was detected in 40.9% (9/22) of benign tumors and in 7.4% (2/27) of the malignant tumors. These results suggest that some of the biological and morphological characteristics of the tumor are associated with canine mammary gland tumors, as also reported for human breast cancer, the possibility of using anti-HER-2/neu antibodies in the treatment of canine mammary tumors.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.12
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• pp.1708-1716
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• 2016

The Akt/mammalian target of the rapamycin (mTOR) pathway is activated in the majority of human cancers. Activation of the Akt/mTOR pathway confers resistance to many types of cancer therapy. In this study, we evaluated the apoptotic effect of ethanol extract of Artemisia annua L. through down-regulation of Akt signal pathways and the mitochondrial pathway in hepato-carcinoma cells (HepG2). A. annua extract is known as a medicinal herb that is effective against cancer. We evaluated anti-proliferative activity by MTT-based viability assay and apoptotic effect by Annexin-V/PI staining, mitochondrial membrane potential (MMP), and caspase-3/7 activity as determined by flow cytometry. A. annua treatment led to loss of MMP, resulting in cytochrome c-inducible activation of caspase-3/7. Treatment with A. annua extract reduced activities of Akt/mTOR/anti-apoptotic proteins (such as Bcl-2 and $Bcl-X_L$), leading to increased activation of tumor suppressor p53 and pro-apoptotic proteins (such as Bax and Bak). We applied LY294002 (inhibitor of Akt) and rapamycin (inhibitor of mTOR) to determine the relationship between signal transduction of proteins associated with apoptosis. LY294002 and rapamycin significantly reduced cell viability and increased apoptosis. These results indicate that Bcl-2 and caspase-3 are key regulators in A. annua extract-induced apoptosis in HepG2 cells and are controlled through the Akt/mTOR signaling pathway.

• Korean Journal of Medicinal Crop Science
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• v.11 no.3
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• pp.195-200
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• 2003

This study was carried out to compare the biological activities of Epjmedium koreanum Nakai grown wild in Korea and China. The antioxidative effect of E. koreanum Nakai-extracts grown wild in Gangwondo was 78%, which was higher than that in China as 71%. The inhibition ratio of growing cancer cells was estimated as 89, 91 and 86% for human liver, lung and breast cancer cell lines, respectively in adding 0.1 g/l of ethanol extracts of E. koreanum grown in Korea. The hepatoprotective effect and Angiotensin Converting Enzyme (ACE) inhibiting effect of Korean one were also observed as 124 and 87%, respectively, which were also higher than those produced in China. There was not much difference between Korean and Chinese one in inhibiting ${\alpha}-glucosidase$ activities in all ranges of supplement. It was proved that most effective extraction solvent was mixed type as water and ethanol (1:1, v/v) to have higher biological activities from both Korean and Chinese ones.

• Journal of Veterinary Clinics
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• v.26 no.1
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• pp.1-7
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• 2009

The Artemisia capillaris THUNB is a perennial herb that belongs to the family Compositae spp and probably the most common plant among the various herbal folk remedies being used in the treatment of abdominal pain, hepatitis, chronic liver disease, jaundice and coughing in Korea. Recently the biological and pharmacological actions of herb have been studied well such as antibacterial, antidiabetic and antitumor activities. This experiment was conducted to investigate antitumor and immunomodulatory effects of Artemisia capillaris extracts against Hepa-1c1c7 and Sarcoma 180 cancer cells in in vivo experimental tests. In in vivo experimental tests using 210 ICR mice, based on flow cytometry, CD3+, CD4+, CD8+ and TNF-${\alpha}+$ splenocytes were significantly (p<0.05) reduced in the Hepa-1c1c7 and Sarcoma 180 inoculated vehicle controls, HP and SP, compared to those of the intact vehicle control on both the $28^{th}$ day and the $42^{nd}$ day, respectively. These decreases of CD3+, CD4+, CD8+ and TNF-${\alpha}+$ cells induced by tumor inoculations were significantly (p<0.05) inhibited by mACH treatment regardless of the type of experiments and tumor cells inoculated. The results suggest that Artemisia capillaris methanol extracts have prominent antitumor effects on the cancer cell lines Hepa-1c1c7 and Sarcoma 180.

• Tuberculosis and Respiratory Diseases
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• v.75 no.2
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• pp.59-66
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• 2013

Background: This study was conducted in order to elucidate the effects of docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors and further tested the role of Prx1 as a predictor for how a patient would respond to docetaxel treatment. Methods: Effects of docetaxel on the growth of scrambled- and shPrx1-infected A549 xenograft tumors in nude mice were measured. Moreover, immunohistochemical expression of Prx1 was evaluated in paraffin-embedded tissues from 24 non-small cell lung cancer patients who had received docetaxel-cisplatin regimens as a first-line treatment. Results: Docetaxel treatment in Prx1 knockdown xenograft tumor resulted in reduced tumors growth compared with other groups. Prx1 knockdown increased the production of cleaved caspases-8 and -9 in the control itself compared to scramble tumors. Moreover, docetaxel treatment in Prx1 knockdown tissue led to an increased protein band. Phosphorylated Akt was found in Prx1 scramble tissues. Phosphorylated FOXO1 was detected in the docetaxel treatment group. On the other hand, Prx1 knockdown completely suppressed the Akt-FOXO1 axis. The median progression-free survival (PFS) of patients with low Prx1 expression was 7 months (95% confidence interval [CI], 6.0-7.7), whereas the median progression-free survival of patients with high Prx1 expression was 4 months (95% CI, 4.0-5.0). However, high Prx1 expression was not associated with decreased PFS (p=0.114). Conclusion: Our findings suggest that elevated Prx1 provides resistance to docetaxel treatment through suppression of FOXO1-induced apoptosis in A549 xenograft tumors, but may not be related with the predictive significance for response to docetaxel treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4031-4036
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• 2012

Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies.

• Journal of Veterinary Clinics
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• v.26 no.5
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• pp.408-412
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• 2009

The Artemisia capillaris THUNB is a perennial herb that belongs to the family Compositae spp. and probably the most common plant among the various herbal folk remedies being used in the treatment of abdominal pain, hepatitis, chronic liver disease, jaundice and coughing in Korea. This experiment was conducted to investigate the effects of Artemisia capillaris extracts on the amounts of splenocytes-derived cytokine ($TNF-{\alpha},\;IL-1{\beta}$ and IL-10). In in vivo experimental tests using 210 ICR mice with Hepa-1c1c7 or sarcoma 180 cancer line, splenocytes derived cytokine contents were significantly (p < 0.05) reduced in the Hepa-1c1c7 and Sarcoma 180 inoculated vehicle controls, HP and SP, compared to those of the intact vehicle control on both the $28^{th}$ day and the $42^{nd}$ day, respectively. However, these decreases of $TNF-{\alpha},\;IL-1{\beta}$ and IL-10 levels induced by tumor inoculations were significantly (p < 0.01, p < 0.05) inhibited by mACH (Artemisia capillaris methanol extracts) treatment regardless of the type of experiments and tumor cells inoculated. The results suggest that Artemisia capillaris methanol extracts have prominent anti-inflammation effects on the cancer cell lines Hepa-1c1c7 and Sarcoma 180.