• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10495-10500
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• 2015

Background: To evaluate the effects of bufalin in A549 human lung adenocarcinoma epithelial cells in vitro and assess the underlying mechanisms. Materials and Methods: Human A549 non-small cell lung cancer (NSCLC) cells were treated with various concentrations of bufalin. Cell proliferation was measured by CCK-8 assay, apoptotic cell percentage was calculated by flow cytometry and morphological change was observed by inverted phase contrast microscopy/transmission electron microscopy. In addition, the membrane potential of mitochondria was detected by JC-1 fluorescence microscopy assay, and the related protein expression of cytochrome C and caspase-3 was analyzed by Western blotting. Results: Bufalin could inhibit the proliferation of A549 cells via induction of apoptosis, with the evidence of characteristic morphological changes in the nucleus and mitochondria. Furthermore, bufalin decreased the mitochondrial membrane potential with up-regulation of cytochrome C in the cytosol, and activation of caspase-3. Conclusions: Bufalin inhibits the proliferation of A549 cells and triggers mitochondria-dependent apoptosis, pointing to therapeutic application for NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1169-1173
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• 2015

Background: Paris polyphylla (Chinese name: Chonglou) had been traditionally used for a long time and shown anti-cancer action. Based on the previous study that paris polyphylla steroidal saponins (PPSS) induced cytotoxic effect in human lung cancer A549 cells, this study was designed to further illustrate the mechanisms underlying. Materials and Methods: The mechanisms involved in PPSS-induced A549 cell death were investigated by phase contrast microscopy and fluorescence microscopy, flow cytometry and western blot analysis, respectively. Results: PPSS decreased the proportion of viable A549 cells, and exposure of A549 cells to PPSS led to both apoptosis and autophagy. Apoptosis was due to activations of caspase-8, caspase-3, as well as cleavage of PARP, and autophagy was confirmed by up-regulation of Beclin 1 and the conversion from LC3 I to LC3 II. Conclusions: PPSS was able to induce lung cancer A549 cell apoptosis and autophagy in vitro, the results underlining the possibility that PPSS would be a potential candidate for intervention against lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1443-1448
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• 2015

To investigate the significance of FOXO3a and Ki67 in human lung adenocarcinomas. Envision immunohistochemical staining and Western blotting were used to examine the protein expression of FOXO3a in 127 cases of human lung adenocarcinoma specimens. The positive rate in lung adenocarcinoma (55.9%) was lower than that in normal tissues (80%). We found that the expression of FOXO3a was closely related with the degree of differentiation, TNM staging, lymph node metastasis and survival. In addition, significant differences in the different pathological types of lung adenocarcinoma cases (P<0.01). The FOXO3a positive rate of the acini as the main type (APA) (86.7%) and the lepidic as the main type (LPA) (82.4%) was higher than the solid as the main type (SPA) (50.0%), the papilla as the main type (PPA) (42.9%) and the micropapilla as the main type (MPA) (9.4%). Moreover, the expression of FOXO3a was negatively related with Ki67 expression. Our results suggested that the expression of FOXO3a is closely correlated with the aggressiveness of lung adenocarcinoma. It was indicated that disregulation of FOXO3a might play key roles in the occurrence and development of lung a denocarcinoma and joint detection of the two markers might play an important role in diagnosing tumors.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.200-200
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• 2002

Cadmium (Cd) is an environmental pollutant and categorized as a human carcinogen, which has a tendency to accumulate in the human body. The level of Cd in renal cortex and liver are good indicators as an index of Cd exposure in general population. Geometric mean concentration of Cd is 27.4 and 3.1 /g wet weight in renal cortex and liver, respectively, in Korean. Cd is toxic to a number of tissues, notably the liver, kidney, testis, lung, lymphoid tissue and lung. (omitted)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.150.2-151
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• 2003

We have focused on various biological activities of acharan sulfate (AS) isolated from the giant African snail Achatina fulica. In a previous study, AS showed antiangiogenic and immunomodulating activity. We also investigated antitumor activity of AS. In vitro AS had no cytotoxicity within 0 to 200 ug/ml in tumor cells such as Lewis lung carcinoma(LLC) , KM1214 (human colon cancer cell) and Caki-1 (human kidney cancer cell) by both MTT and SRB assay. In vivo AS was used to treat C57BL/6 mice bearing LLC by subscutaneous injection. (omitted)

• Tuberculosis and Respiratory Diseases
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• 제45권5호
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• pp.984-991
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• 1998

연구배경: 폐암을 포함한 여러 종양에서 3p의 allelic loss가 매우 흔하게 관찰된다는 것은 널리 알려진 사실이다. 따라서 이 구역에 암억제유전자가 존재할 가능성이 높다고 생각되어 과거부터 이에 대한 연구가 활발하게 진행되고 있다. 하지만 현재까지는 몇몇 후보 유전자들이 밝혀져 있을 뿐, 확실한 암억제유전자를 규명해내지는 못하고 있는 실정이다. FHIT(Fragile Histidine Triad) 유전자는 최근 주목을 받고 있는 후보 암억제유전자로서 3p14.2에 위치하고 있으며 식도, 위, 두경부암 등의 여러 종양에서 이 위치의 homozygous deletion이 보고된 바 있다. 서열 분석상 이 유전자는 human genome 중 손상에 가장 취약한 곳중 하나인 FRA3B fragile site와 신세포암에서 잘 발견되는 t(3;8) chromosomal translocation의 breakpoint를 포함하고 있다. 이러한 구조적 특정과 함께 폐암에서 3p의 allelic loss가 특히 높은 빈도로 나타난다는 점에 주목하여, 연자들은 폐암 세포주를 대상으로 FHIT 유전자의 발현 이상을 살펴봄으로써 암억제유전자로서의 가능성을 평가하고자 하였다. 방 법: 총 21개 세포주(비소세포폐암 : 16, 소세포폐암 : 5)를 배양하여 RNA를 분리하였고 reverse transcription을 시행하여 single-strand cDNA를 합성하였다. 이후 FHIT 유전자의 exon 5에서 exon 9에 해당하는 coding region을 PCR로 증폭하였다. 이 PCR product를 ethidium bromide로 염색된 1.5 % agarose gel에서 전기영동시킨 후 band를 관찰하였다. 결 과: 총 21개 폐암 세포주중 12개(57%) 세포주에서 비정상적인 band가 관찰되거나(3개), band가 관찰되지 않았다(9개). 16개의 비소세포폐암 세포주중 7개 (44%)에서 비정상적인 band가 관찰되거나(2개), band가 관찰되지 않았다(5개). 5개의 소세포폐암 세포주에서는 5개(100%) 모두에서 비정상적인 band가 관찰되거나(1개), band가 관찰되지 않았다 (4개). 결 론: 이러한 결과를 살펴볼 때, FHIT 유전자의 발현 이상은 폐암, 특히 소세포폐암에서 높은 빈도로 관찰되었으며, 이는 FHIT 유전자가 폐암 발생에 있어서 중요한 암억제유전자일 것이라는 가설을 뒷받침하는 소견이라 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제61권6호
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• pp.578-584
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• 2006

저자들은 뚜렷한 종양성 병변이 방사선학적으로는 물론 전신 PET에서도 유일하게 폐에서만 발견이 되었고, 산부인과적 검진 및 골반 MRI 검사에서도 원발성 종양을 의심할만한 병변이 발견되지 않았으며, 병리학적으로 면역조직화학염색을 통해 ${\beta}$-HCG에 양성인 원발성 폐 융모막암종의 증례를 경험하였기에 이 환자의 임상적 소견과 경과를 문헌 고찰과 함께 보고하는 바이다.

• 대한약침학회지
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• 제7권2호
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• pp.5-17
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• 2004

Objective : In order to measure the efficacy of cultivated wild ginseng distilled herbal acupuncture by concentration level, we've treated A549 human lung cancer lines with different concentrations of cultivated wild ginseng distilled herbal acupuncture and examined mRNA and proteins which take parts in apoptosis. Methods : A549 human lung cancer lines were treated with various concentration levels of cultivated wild ginseng distilled herbal acupuncture and cell toxicity was carefully examined. From the analysis of DNA fragmentation, RT-PCR and Western blot, manifestation of mRNA and proteins which are associated with apoptosis were inspected. Results : The following results were obtained on apoptosis of A549 human lung cancer lines after administering various concentration levels of cultivated wild ginseng distilled herbal acupuncture. 1. Measuring cell toxicity of lung cancer cells, strong cell toxicity was detected at high concentration level(1000ul, 1200ul), but no consistent concentration dependent reliance was detected. 2. Through DNA fragmentation, we were able to confirm cell destruction in all groups. 3. Experiment groups treated with cultivated wild ginseng distilled herbal acupuncture showed inhibition of Bcl-2 and COX-2 at mRNA and Protein level, whileas increase of Bax was shown. 4. Manifestation of p21, p53, Cyclin E, and Cyclin Dl were confirmed in all groups. 5. Extrication of Cytochrome C was detected at all groups, as well as increased activity of the enzyme caspase-3 and caspase-9, and PARP fragmentation were confirmed. Conclusion : According to the results, we can carefully deduce cell destruction of A549 human lung cancer lines were induced by Apoptosis. At the fixed level, cultivated wild ginseng distilled herbal acupuncture showed decrease of Bcl-2 and COX-2, as well as increase of Bax. Since cultivated wild ginseng distilled herbal acupuncture increases manifestation of p21, p53, Cyclin E, and Cyclin Dl, it affects cellular cycle and through these phenomena, we can consider extrication of Cytochrome C, increase of caspase, and PARP fragmentation are the results.

• Biomolecules & Therapeutics
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• 제20권6호
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• pp.538-543
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• 2012

The Maillard Reaction Products (MRPs) are chemical compounds which have been known to be effective in chemoprevention. Death receptors (DR) play a central role in directing apoptosis in several cancer cells. In our previous study, we demonstrated that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal, a MRP product, inhibited human colon cancer cell growth by inducing apoptosis via nuclear factor-${\kappa}B$ (NF-${\kappa}B$) inactivation and $G_2$/M phase cell cycle arrest. In this study, (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate, a new (E)-2,4-bis(p-hydroxyphenyl)-2-butenal derivative, was synthesized to improve their solubility and stability in water and then evaluated against NCI-H460 and A549 human lung cancer cells. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate reduced the viability in both cell lines in a time and dose-dependent manner. We also found that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate increased apoptotic cell death through the upregulation of the expression of death receptor (DR)-3 and DR6 in both lung cancer cell lines. In addition to this, the transfection of DR3 siRNA diminished the growth inhibitory and apoptosis inducing effect of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate on lung cancer cells, however these effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate was not changed by DR6 siRNA. These results indicated that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal diacetate inhibits human lung cancer cell growth via increasing apoptotic cell death by upregulation of the expression of DR3.

• Journal of Acupuncture Research
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• 제21권6호
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• pp.1-17
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• 2004

Objective : To compare and examine how adjustment of pH and electrolyte can affect the efficacy of cultivated wild ginseng distilled herbal acupuncture, we've administered pure cultivated wild ginseng distilled herbal acupuncture and pH and electrolyte adjusted cultivated wild ginseng distilled herbal acupuncture on A549 human lung cancer lines. Then mRNA and proteins which take parts in apoptosis were examined. Methods : Pure cultivated wild ginseng distilled herbal acupuncture treated group was set as the control group and pH and electrolyte adjusted cultivated wild ginseng distilled herbal acupuncture groups were administered on A549 human lung cancer lines. Cell toxicity was carefully examined and from the analysis of DNA fragmentation, RT-PCR, and Western blot, manifestation of mRNA and proteins which are associated with apoptosis were inspected. Results : The following results were obtained on apoptosis of A549 human lung cancer lines after administering pH and electrolyte adjusted cultivated wild ginseng distilled herbal acupuncture. 1. Measuring cell toxicity of lung cancer cells, higher cell toxicity was detected at pH and electrolyte adjusted groups and the results were concentration dependent. 2. Through DNA fragmentation, we were able to confirm cell destruction in all groups. 3. Experiment groups treated with cultivated wild ginseng distilled herbal acupuncture showed inhibition of Bcl-2 and COX-2 at mRNA and Protein level, whileas increase of Bax was shown. 4. Manifestation of p21, p53, Cyclin E, and Cyclin D1 were confirmed in all groups. 5. Extrication of Cytochrome C was detected at all groups, as well as increased activity of the enzyme caspase-3 and caspase-9, and PARP fragmentation were confirmed. Conclusions : From the above results, we can carefully deduce cell destruction of A549 human lung cancer lines were induced by Apoptosis. At the same concentration level, cell destruction efficacy was better with adjusted pH and electrolyte. Cultivated wild ginseng distilled herbal acupuncture also showed decrease of Bcl-2 and COX-2, as well as increase of Bax. Since cultivated wild ginseng distilled herbal acupuncture increases manifestation of p21, p53, Cyclin E, and Cyclin D1, it affects cellular cycle and through these phenomena, we can consider extrication of Cytochrome C, increase of caspase, and PARP fragmentation are the results.