• The Korean Journal of Physiology and Pharmacology
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• 제22권1호
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• pp.43-51
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• 2018

Although cisplatin is one of the most effective antitumor drugs for ovarian cancer, the emergence of chemoresistance to cisplatin in over 80% of initially responsive patients is a major barrier to successful therapy. The precise mechanisms underlying the development of cisplatin resistance are not fully understood, but alteration of DNA methylation associated with aberrant gene silencing may play a role. To identify epigenetically regulated genes directly associated with ovarian cancer cisplatin resistance, we compared the expression and methylation profiles of cisplatin-sensitive and -resistant human ovarian cancer cell lines. We identified ${\alpha}$-N-acetylgalactosaminidase (NAGA) as one of the key candidate genes for cisplatin drug response. Interestingly, in cisplatin-resistant cell lines, NAGA was significantly down-regulated and hypermethylated at a promoter CpG site at position +251 relative to the transcriptional start site. Low NAGA expression in cisplatin-resistant cell lines was restored by treatment with a DNA demethylation agent, indicating transcriptional silencing by hyper-DNA methylation. Furthermore, overexpression of NAGA in cisplatin-resistant lines induced cytotoxicity in response to cisplatin, whereas depletion of NAGA expression increased cisplatin chemoresistance, suggesting an essential role of NAGA in sensitizing ovarian cells to cisplatin. These findings indicate that NAGA acts as a cisplatin sensitizer and its gene silencing by hypermethylation confers resistance to cisplatin in ovarian cancer. Therefore, we suggest NAGA may be a promising potential therapeutic target for improvement of sensitivity to cisplatin in ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4651-4654
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• 2013

Choroquine (CQ) and valproic acid (VPA) have been extensively studied for biological effects. Here, we focused on efficacy of combined CQ and VPA on osteosarcoma cell lines. Viability of osteosarcoma cell lines (U20S and HOS) was analyzed by MTT assay. Apoptotic assays and colony formation assays were also applied. ROS generation and Western Blotting were performed to determine the mechanism of CQ and VPA combination in the process of apoptosis. The viability of different osteosarcoma cell lines significantly decreased after CQ and VPA combination treatment compared with either drug used alone, and apoptosis was increased significantly. ROS generation was triggered leading to expression of apoptosis related genes being increased and of antiapoptotic related genes being decreased. From our data shown here, CQ and VPA combination treatment in vitro enhanced cytotoxicy to osteosarcoma cells.

• Applied Microscopy
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• 제38권3호
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• pp.245-250
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• 2008

전립선암은 남성 사망의 주된 원인이 되는 치명적인 질병으로 남성호르몬 의존형과 비의존형이 있다. Etoposide (Eto)는 현재 전립선암을 치료하는 데 사용하고 있으나 남성호르몬 비의존형에는 치료 성공률이 낮아서, 보다 효과적인 치료제 개발이 절실히 요구되어왔다. 본 연구는 항산화제인 vitamin C (VC)가 전립선 암세포에 어떠한 역할을 하는지 알아보고자 남성호르몬 의존형-전립선 암세포인 LNCaP와 비의존형 암세포인 DU-145에 비교적 낮은 농도의 Eto와 VC를 복합처리한 결과, Eto만을 투여한 것과 비교하여 암세포의 성장이 현저하게 억제되었고, apoptosis의 발생률 역시 유의적으로 증가하였다(p<0.05). 이러한 결과는 VC가 전립선암 치료제로 사용하고 있는 Eto의 효과를 증가시킬 수 있음을 강력히 시사하는 것이다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5513-5518
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• 2013

IFN-${\gamma}$ plays an indirect anti-cancer role through the immune system but may have direct negative effects on cancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferation and how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-${\gamma}$ and found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-${\gamma}$ on apoptosis of cell lines and no effect on cell aging as assessed by ${\beta}$-gal staining. Microarray assay revealed that IFN-${\gamma}$ changed the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well as chemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-${\gamma}$ arrested the cells in the G1/S phase. IFN-${\gamma}$ may slow proliferation of some gastric cancer cells by affecting the cell cycle to play a negative role in the development of gastric cancer.

• Archives of Pharmacal Research
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• 제19권4호
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• pp.261-263
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• 1996

SK-302B, an antibiotic purified from soil Streptomyces sp. 302, was structurally identified as echinomycin (C/sub 50/H/sub 66/N/sub 11/S/sub 2/). In the present experiment, the possibility of SK-302B as an anticolon cancer agent was investigated by using chemosensitivity system (MTT assay, clonogenic assay). Treatment of SK-302B on various colon cancer cell lines resulted in a significant cytotoxicity and tumor colony formation inhibition. These studies showed that SK-302B had a potent inhibition on colon cancer cells.

• 한국식품영양과학회지
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• 제29권5호
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• pp.870-874
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• 2000

This study was designed to investigate the cytotoxic effect of methanol extract of garlic, onion and those mixture on two kinds of human lung cancer cell lines (NCI-H522, NCI-H596) using MTT assay. MeOH extract of garlic, onion and those mixture showed cytotoxic effect on both NCI_H522 and NCI-H596. The growth of the cancer cells exposed to medium containing garlic, onion extracts and those mixture was inhibited dose-dependently. The growth of NCI-H522 was inhibited more in the garlic extract than in the onion extract, but that of HCI-H596 was inhibited highese in the onion extract. IC50 values of garlic extract on NCI-H522 and NCI-H596 were 0.84 mg/mL, 0.88 mg/mL and those of onion extract were 1.04 and 0.79, respectively. and the mixture of garlic and onion extracts also inhibited the growth of both NCI-H522 and NCI-H596 cells.

• 대한두경부종양학회:학술대회논문집
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• 대한두경부종양학회 1991년도 제8차 학술대회 연제순서 및 초록집
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• pp.22.2-24
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• 1991

• Molecules and Cells
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• 제37권12호
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• pp.888-898
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• 2014

Pancreatic cancer is one of the most fatal cancers and is associated with limited diagnostic and therapeutic modalities. Currently, gemcitabine is the only effective drug and represents the preferred first-line treatment for chemotherapy. However, a high level of intrinsic or acquired resistance of pancreatic cancer to gemcitabine can contribute to the failure of gemcitabine treatment. To investigate the underlying molecular mechanisms for gemcitabine resistance in pancreatic cancer, we performed label-free quantification of protein expression in intrinsic gemcitabine-resistant and -sensitive human pancreatic adenocarcinoma cell lines using our improved proteomic strategy, combined with filter-aided sample preparation, single-shot liquid chromatography-mass spectrometry, enhanced spectral counting, and a statistical method based on a power law global error model. We identified 1931 proteins and quantified 787 differentially expressed proteins in the BxPC3, PANC-1, and HPDE cell lines. Bioinformatics analysis identified 15 epithelial to mesenchymal transition (EMT) markers and 13 EMT-related proteins that were closely associated with drug resistance were differentially expressed. Interestingly, 8 of these proteins were involved in glutathione and cysteine/methionine metabolism. These results suggest that proteins related to the EMT and glutathione metabolism play important roles in the development of intrinsic gemcitabine resistance by pancreatic cancer cell lines.

• Food Science and Biotechnology
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• 제15권3호
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• pp.369-373
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• 2006

Water extracts obtained from cultured mountain ginseng (CMG) were evaluated for their ability to stimulate immune cells and inhibit cancer cell proliferation. The lymphocyte subpopulation in mouse splenocytes in vivo was significantly increased by the administration of the CMG extract (27.4 mg/mouse). Interleukin-2 and ${\gamma}$-interferon in the mice serum increased up to 30% in CMG extract-treated mice. At a concentration of 1.37 mg/mL, nitric oxide increased up to 400% in the macrophage cell line treated with CMG extract. The CMG extract significantly retarded the proliferation of human acute promyelocytic (HL60), human histiocytic (U937), and mouse lymphocytic (L1210) leukemia cell lines in vitro at concentrations over 2.74-13.7 mg/mL. In addition, CMG extract treatments (1.37 mg/mL and 2.74 mg/mL) lead to the increased expression of the p53 gene and protein in cultured U937 leukemia cell lines. These results indicate that water extracts of CMG are capable of both immune cell stimulation and cancer cell growth inhibition.

• Journal of Chest Surgery
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• 제50권3호
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• pp.153-162
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• 2017

Background: The mesenchymal-epithelial transition factor (MET) receptor can be overexpressed in solid tumors, including small cell lung cancer (SCLC). However, the molecular mechanism regulating MET stability and turnover in SCLC remains undefined. One potential mechanism of MET regulation involves the C-terminus of Hsp70-interacting protein (CHIP), which targets heat shock protein 90-interacting proteins for ubiquitination and proteasomal degradation. In the present study, we investigated the functional effects of CHIP expression on MET regulation and the control of SCLC cell apoptosis and invasion. Methods: To evaluate the expression of CHIP and c-Met, which is a protein that in humans is encoded by the MET gene (the MET proto-oncogene), we examined the expression pattern of c-Met and CHIP in SCLC cell lines by western blotting. To investigate whether CHIP overexpression reduced cell proliferation and invasive activity in SCLC cell lines, we transfected cells with CHIP and performed a cell viability assay and cellular apoptosis assays. Results: We found an inverse relationship between the expression of CHIP and MET in SCLC cell lines (n=5). CHIP destabilized the endogenous MET receptor in SCLC cell lines, indicating an essential role for CHIP in the regulation of MET degradation. In addition, CHIP inhibited MET-dependent pathways, and invasion, cell growth, and apoptosis were reduced by CHIP overexpression in SCLC cell lines. Conclusion: C HIP is capable of regulating SCLC cell apoptosis and invasion by inhibiting MET-mediated cytoskeletal and cell survival pathways in NCI-H69 cells. CHIP suppresses MET-dependent signaling, and regulates MET-mediated SCLC motility.