• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권2호
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• pp.110-122
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• 2005

Adenoid cystic carcinoma (ACC) of salivary glands has a protracted clinical course with perineural invasion, delayed onset of hematogenous metastasis, and poor responses to classical cytotoxic chemotherapic agents. Most deaths from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the dissemination of metastatic cells is important for the design of more effective therapy of salivary cancer. I determined in vitro expression of epidermal growth factor receptor (EGFR) and its downstream effectors and vascular endothelial growth factor receptor (VEGFR)-2 on a human salivary ACC cell line (ACC2). I also evaluated the expression of EGF and VEGF signaling molecules and metastasis-related proteins on human salivary ACC cells orthotopically growing in nude mice. In Western blot and immunohistochemical analyses, EGFR and VEGFR-2 were presented and phosphorylated in ACC2 cells. In human parotid cancer xenografts in nude mice, EGF and VEGF signaling molecules, IL-8, and MMP-9 were expressed at markedly higher levels than in normal parotid tissues. Moreover, tumor-associated endothelial cells of this orthotopic parotid tumor expressed phosphorylated VEGFR-2 and phosphorylated Akt, which is a cell-survival protein. These data show that those biomarkers can be molecular targets for therapy of salivary ACC, which has a propensity for delayed lung metastasis.

• 동의생리병리학회지
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• 제17권1호
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• pp.183-189
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• 2003

Platycodi Radix, the root of Platycodon grandiflorum, commonly known as Doraji, is used as a traditional oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. We investigated the effects of an aqueous extract from the roots of P. grandiflorum (AEPG) on the cell proliferation of human lung carcinoma A549 cells in order to understand its anti-proliferative mechanism. AEPG treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner. This anti-proliferative effect of A549 cells by AEPG treatment was associated with morphological changes such as membrane shrinking, cell rounding up and inhibition of cell migration. DNA flow cytometric histograms showed that populations of both Sand G2/M phase of the cell cycle were increased by AEPG treatment in a concentration-dependent manner. AEPG treatment induced a marked accumulation of tumor suppressor p53 and a concomitant induction of cyclin-dependent kinase (Cdk) inhibitor p21 and p27. In addition, SSS treatment resulted in down-regulation of Cdk2 and Cdk4 expression. The present results indicated that AEPG-induced inhibition of lung cancer cell proliferation is associated with the blockage of S to G2/M phase progression the induction of apoptosis. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention against human lung cancer.

• Tuberculosis and Respiratory Diseases
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• 제71권5호
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• pp.363-367
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• 2011

Lymphoepithelioma-like carcinoma (LELC) of the lung is a very rare tumor. Originally described in the nasopharynx as lymphoepithelioma, this carcinoma has also been found in the stomach, esophagus, thymus, cervix, urinary bladder, skin, and salivary glands. Histologically, it is an undifferentiated carcinoma that has a syncytial appearance with tumor cells and is infiltrated by numerous lymphocytes, macrophages, and plasma cells. LELC of the lung occurs more commonly in Asians, particularly Chinese. Many studies have reported the association between Epstein-Barr virus (EBV) and LELC of the lung in Asian patients. A 45-year-old man had a solitary pulmonary nodule on a routine chest X-ray examination. As a malignant tumor was suspected, surgical resection was performed to establish the correct diagnosis. The pathology of the excised tumor demonstrated LELC of the lung. This is the first report of LELC of the lung in Korea.

• 동의생리병리학회지
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• 제19권3호
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• pp.722-728
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• 2005

The DNA topoismerase I inhibitor ${\beta}-lapachone$, the product of a lapacho tree (Tabebuia avellanedae) from South America, activates a novel apoptotic response in a number of cell lines. In the present report, we investigated the effects of ${\beta}-lapachone$ on the growth of human lung in human non-small-cell-lung-cancer A549 cells. Upon treatment with ${\beta}-lapachone$, a concentration-dependent inhibition of cell viability and cell proliferation was observed as measured by hemocytometer counts and MTT assay. The ${\beta}-lapachone-treated$ cells developed many of the hallmark features of apoptosis, including membrane shrinking, condensation of chromatin and DNA fragmentation. These apoptotic effects of ${\beta}-lapachone$ in A549 cells were associated with a marked induction of pro-apoptotic Bax expression, however the levels of anti-apoptotic Bcl-2 expression were decreased in a dose-dependent manner. Accordingly, elevated amount of cyclin-dependent kinase inhibitor p21 expression accompanied by up-regulation of tumor suppressor p53 was observed. By RT-PCR analyses, decrease in gene expression level of telomerase reverse transcriptase and telomeric repeat binding factor were also observed. Thus, these findings suggest that ${\beta}-lapachone$ may be a potential anti-cancer therapeutics for the control of human lung cancer cell model.

• Journal of Microbiology and Biotechnology
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• 제32권7호
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• pp.918-926
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• 2022

Proteins related to DNA replication have been proposed as cancer biomarkers and targets for anticancer agents. Among them, minichromosome maintenance (MCM) proteins, often overexpressed in various cancer cells, are recognized both as notable biomarkers for cancer diagnosis and as targets for cancer treatment. Here, we investigated the activity of cedrol, a single compound isolated from Juniperus chinensis, in reducing the expression of MCM proteins in human lung carcinoma A549 cells. Remarkably, cedrol also strongly inhibited the expression of all other MCM protein family members in A549 cells. Moreover, cedrol treatment reduced cell viability in A549 cells, accompanied by cell cycle arrest at the G1 phase, and enhanced apoptosis. Taken together, this study broadens our understanding of how cedrol executes its anticancer activity while demonstrating that cedrol has potential application in the treatment of human lung cancer as an inhibitor of MCM proteins.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5983-5987
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• 2013

Radix Tetrastigma Hemsleyani Flavone (RTHF) is widely used as a traditional herb for its detoxification and anti-inflammation activity. Recently, several studies have shown that RTHF can inhibit growth and induce apoptosis in human cancer cell lines. However, the mechanisms are not completely understood yet. In this study we investigated the potential effects of RTHF on growth and apoptosis in human lung adenocarcinoma A549 cells as well as its mechanisms. A549 cells were treated with RTHF at various concentrations for different times. In vitro the MTT assay showed that RTHF had obvious anti-proliferation effects on A549 cells in a dose- and time-dependent manner. Cell morphological changes observed by inverted microscope and Hoechst33258 methods were compared with apoptotic changes observed by fluorescence microscope. Cell apoptosis inspected by flow cytometry showed significant increase in the treatment group over the control group (P<0.01). Expression of apoptosis related Bax/Bcl-2, caspases and MAPK pathway proteins were detected by Western blotting. The results showed that RTHF up-regulated the Bax/Bcl-2 ratio and cle-caspase3/9, cle-PARP expression in a dose-dependent manner. Expression of p-p38 increased, p-ERK decreased significantly and that of p-JNK was little changed in the RTHF group when compared with the control group. These results suggest that RTHF might exert anti-growth and apoptosis activity against lung cancer A549 cells through activation of caspases and Bcl-2 family proteins and the MAPK pathway, therefore presenting as a promising therapeutic agent for the treatment of lung cancer.

• 동의생리병리학회지
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• 제21권4호
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• pp.907-915
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• 2007

In this study the effect of water extract of Sophora tonkinensis Gapnep (RST) was investigated on the growth of human lung carcinoma A549 cells. Exposure of A549 cells to RST resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay. The antiproliferative effect by RST treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. RST treatment did not induce the cell cycle arrest and the levels of tumor suppressor p53 as well as cyclin-dependent kinase inhibitor p21(WAF1/CIP1). It was found that RST treatment decreased the levels of cyclooxygenase (COX) -2 mRNA and protein expression without significant changes in the expression of COX-1 and inducible nitric oxide synthase (iNOS), which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. RST treatment also slightly inhibited the levels of human telomerase reverse transcriptase (hTERT) mRNA and protein expression, and the activity of telomerase. Taken together, these findings suggested that RST-induced inhibition of human lung carcinoma A549 cell growth was aoosciated with the inhibition of COX-2 expression and PGE2 production. These results provided important new insights into the possible molecular mechanisms of the anti-cancer activity of RST.

• Journal of Ginseng Research
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• 제22권1호
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• pp.18-21
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• 1998

Comparative cytotoxic activities of petroleum ether soluble fraction from various ginsengs of Panax species were evaluated using A549 (human lung adenocarcinoma) and SK-OV-3(human ovary carcinoma) cancer cell lines. Korean red ginseng, Korean white ginseng, American ginseng and Canadian ginseng were found to show more potent cytotoxicitles on A549 and SK-OV-3 cell lines than Chinese red ginseng, Japanese red ginseng and Sanchi ginseng. It is noteworthy that especially, red ginseng prepared from the root of Panax ginseng cultivated in Korea shows relatively stronger cytotoxic activities than those cultivated in China and Japan.

• 대한의생명과학회지
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• 제28권4호
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• pp.247-259
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• 2022

Immunotherapy, which uses an immune mechanism in the body, has received considerable attention for cancer treatment. Suberoylanilide hydroxamic acid (SAHA), also known as a histone deacetylase inhibitor (HDACi), is used as a cancer treatment to induce active immunity by increasing the expression of T cell-induced chemokines. However, this SAHA treatment has the disadvantage of causing PD-L1 overexpression in tumor cells. In this study, we prevented PD-L1 overexpression by blocking the PD-1/PD-L1 pathway using PD-L1 siRNA. We designed two types of liposomes, the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC) for SAHA, and 1,2-dioleoyl-3-trimethylammoniumpropane (DOTAP) for siRNA. To effectively target PD-L1 in cancer cells, we conjugated PD-L1 antibody with liposomes containing SAHA or PD-L1 siRNA. These immunoliposomes were also evaluated for cytotoxicity, gene silencing, and T-cell-induced chemokine expression in human non-small cell lung cancer A549 cells. It was confirmed that the combination of the two immunoliposomes increased the cancer cell suppression efficacy through Jurkat T cell induction more than twice compared to SAHA alone treatment. In conclusion, this combination of immunoliposomes containing a drug and nucleic acid has promising therapeutic potential for non-small-cell lung carcinoma (NSCLC).

• Journal of Acupuncture Research
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• 제20권5호
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• pp.93-106
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• 2003

Objective : To investigate the possible molecular mechanism(s) of melittin as a candidate of anti-cancer drug, we examined the effects of the compound on the growth of human lung carcinoma cell line A549. Methods: MTT, morphological changes, DAPI staining, Western blot, RT-PCR and in vitro prostaglandin E2 (PGE2) accumulation assays were performed. Results: The anti-proliferative effect by melittin treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. Melittin induced apoptotic cell death in a concentration-dependent manner, which was associated with inhibition or degradation of apoptotic target proteins such as ${\beta}$-catenin, poly(ADP-ribose) polymerase(PARP) and phospholipase $C-{\gamma}1(PLC-{\gamma}1)$. Melittin treatment inhibited the expression of cyclooxygenase-2(COX-2) and accumulation of PGE2 in aconcentration-dependent fashion. In addition, Melittin treatment induced the down-regulation of telomerase reverse transcriptase(hTERT) and proto-oncogene c-myc expression of A549 cells. Conclusions: Taken together, these findings suggest that melittin-induced inhibition of human lung cancer cell proliferation is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products, and melittin may have therapeutic potential in human lung cancer.