• Title/Summary/Keyword: Lung Cancer

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Anticancer Activity of Novel Daphnane Diterpenoids from Daphne genkwa through Cell-Cycle Arrest and Suppression of Akt/STAT/Src Signalings in Human Lung Cancer Cells

  • Jo, Si-Kyoung;Hong, Ji-Young;Park, Hyen Joo;Lee, Sang Kook
    • Biomolecules & Therapeutics
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    • v.20 no.6
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    • pp.513-519
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    • 2012
  • Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the $IC_{50}$ values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers.

Knockdown of Med19 Suppresses Proliferation and Enhances Chemo-sensitivity to Cisplatin in Non-small Cell Lung Cancer Cells

  • Wei, Ling;Wang, Xing-Wu;Sun, Ju-Jie;Lv, Li-Yan;Xie, Li;Song, Xian-Rang
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.875-880
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    • 2015
  • Mediator 19 (Med19) is a component of the mediator complex which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II. Accumulating evidence has shown that Med19 plays important roles in cancer cell proliferation and tumorigenesis. The involvement of Med19 in sensitivity to the chemotherapeutic agent cisplatin was here investigated. We employed RNA interference to reduce Med19 expression in human non-small cell lung cancer (NSCLC) cell lines and analyzed their phenotypic changes. The results showed that after Med19 siRNA transfection, expression of Med19 mRNA and protein was dramatically reduced (p<0.05). Meanwhile, impaired growth potential, arrested cell cycle at G0/G1 phase and enhanced sensitivity to cisplatin were exhibited. Apoptosis and caspase-3 activity were increased when cells were exposed to Med19 siRNA and/or cisplatin. The present findings suggest that Med19 facilitates tumorigenic properties of NSCLC cells and knockdown of Med19 may be a rational therapeutic tool for lung cancer cisplatin sensitization.

Genetic Variation in PDCD6 and Susceptibility to Lung Cancer

  • He, Yan-Qi;Zhou, Bin;Shi, Shao-Qing;Zhang, Lin;Li, Wei-Min
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4689-4693
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    • 2012
  • Lung cancer is the most common type of cancer and one of the leading causes of death in the world. Genetic factors play an important role in its development. PDCD6, the encoding gene for programmed cell death protein 6, may function as a tumor suppressor gene. Non-small cell lung cancer (NSCLC) contributes about 80% to newly histologically diagnosed lung cancer patients. To explore the relationship between PDCD6 and NSCLC, we examined two single nucleotide polymorphisms(rs3756712 G/T andrs4957014 G/T, both in the intron region) of the PDCD6gene.A hospital-based case-control study was carried out including 302 unrelated NSCLC patients and 306 healthy unrelated subjects. Significantly increased NSCLC risk was found to be associated with the T allele of rs4957014 (P=0.027, OR=0.760, 95%CI=0.596-0.970). The genotype and allele frequencies of rs3756712 did not shown any significant difference between NSCLC group and controls (P=0.327, OR=0.879, 95%CI=0.679-1.137). In conclusion, we firstly demonstrated the association between the PDCD6 gene and risk of NSCLC in a Chinese Han population.

Kanahia Laniflora Methanolic Extract Suppressed Proliferation of Human Non-Small Cell Lung Cancer A549 Cells

  • Alfaif, Mohammad Yahya
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.10
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    • pp.4755-4759
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    • 2016
  • Introduction: Lung cancer is one of the most common cancers worldwide. In certain countries such as United States of America, it is the leading cause of related cancer mortality among both men and women. Natural products play an important role in overcoming the limitations of chemotherapy and radiotherapy. Objectives: In this study, we investigated the antiproliferative and apoptotic activities of Kanahia laniflora methanolic extract against human non-small cell lung cancer cells (A549). Methods: Sulforhodamine B colorimetric assays were used to determine the inhibitory effects of a leaf methanolic extract against A549 cells. Results: The extract showed strong cytotoxic activity against A549 cells with an $IC_{50}$ value of $0.13{\mu}g/ml$ compared to $0.21{\mu}g/ml$ for doxorubicin. The extract also significantly increased the percentage of apoptotic cells to 49.7% as compared to 1.4% and 47.4% for control and doxorubicin respectively. Conclusion: These results showed, for the first time, that a methanolic extract of Kanahia laniflora leaves can inhibit the proliferation of human non-small cell lung cancer cells (A549). Further attention to its potential as a new effective anticancer agent is warranted.

Steroidal Saponins from Paris polyphylla Induce Apoptotic Cell Death and Autophagy in A549 Human Lung Cancer Cells

  • He, Hao;Sun, Yan-Ping;Zheng, Lei;Yue, Zheng-Gang
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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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.

An Ecological Study of Lung Cancer Mortality and Severe Air Pollution in the 1960s in an Industrial City in Japan

  • Shima, Masayuki;Yoda, Yoshiko
    • Asian Journal of Atmospheric Environment
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    • v.3 no.1
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    • pp.9-18
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    • 2009
  • This study aimed at assessing the association between exposure to severe air pollution in the past and the subsequent transition in lung cancer mortality among persons who lived in an industrial city. Vital statistics from 1983 to 2006 and the data on air pollution measurements from 1960 to 1990 in Amagasaki City, Japan, were used. Pearson correlation coefficients were calculated between the standardized mortality ratios (SMRs) for lung cancer and the air pollution levels in 6 wards of Amagasaki City. The associations between changes in air pollution levels and the annual SMRs were also evaluated in the light of a potential latency period. The levels of air pollution were extremely high in the 1960s, and they decreased since 1970. The SMRs for lung cancer in 1989-1993 among females for 6 wards were significantly associated with the amounts of both sulfur oxides and dust fall in the past for each ward. The positive associations were observed between the annual SMRs among females and the amounts of both pollutants when the lag time of 20-30 years was taken into account. These results suggest that severe air pollution in the 1960s in an industrial city affected the subsequent increase in lung cancer mortality.

Relationships among Uncertainty, Distress, and Quality of Life in Lung Cancer Patients: Mediating effect of Resilience (폐암 환자의 불확실성과 디스트레스가 삶의 질에 미치는 영향: 극복력의 조절효과)

  • Lee, Jungah;Kim, Minju
    • Journal of muscle and joint health
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    • v.25 no.2
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    • pp.148-156
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    • 2018
  • Purpose: The purposes of this study were to examine health-related quality of life and to identify the mediating effect of resilience on the relationship among uncertainty, distress, and health-related quality of life in lung cancer patients. Methods: A total of 149 lung cancer patients visiting the D hospital in B city completed a questionnaire, including demographic and disease-specific characteristics, uncertainty, distress, resilience, and health-related quality of life. Data were analyzed with descriptive analysis, t-tests, ANOVA, and multiple regression analyses via SPSS 24. Results: Health-related quality of life was $81.00{\pm}21.39$ (range 0~136) in lung cancer patients. In the results of hierarchical regression analyses, the health-related quality of life was associated with education, uncertainty, distress, and resilience. However, there was no mediating effect of resilience on the relationship among uncertainty, distress, and health-related quality of life. Conclusion: Lung cancer patients with high uncertainty and distress and low resilience could experience low health-related quality of life. In order to reduce uncertainty and distress, it is necessary to provide more detailed, systematic information and support, while reinforcing positive thinking.

Inhibitory Effect of Bee Venom Toxin on Lung Cancer NCI H460 Cells Growth Through Induction of Apoptosis via Death Receptor Expressions

  • Hur, Keun Young;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.31 no.1
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    • pp.121-130
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    • 2014
  • Objectives : I investigated whether bee venom inhibit cell growth through enhancement of death receptor expressions in the human lung cancer cells, NCI-H460. Methods : Bee venom(1-5 ${\mu}g/ml$) inhibited the growth of NCI-H460 lung cancer cells by the induction of apoptotic cell death in a dose dependent manner. Results : Consistent with apoptotic cell death, expression of TNF-R1, TNF-R2, FAS, death receptors(DR) 3, 4, 5 and 6 was increased in the cells. Expression of DR downstream pro-apoptotic proteins including Caspase-8, -3, -9 was upregulated and Bax was concomitantly overwhelmed the expression of Bcl-2. NF-kB were inhibited by treatment with bee venom in NCI-H460 cells through TNF response change led by TNF-R1 and TNF-R2. Conclusions : These results suggest that bee venom should exert anti-tumor effect through induction of apoptotic cell death in NCI-H460 human lung cancer cells via enhancement of death receptor expression, and that bee venom could be a promising agent for preventing and treating lung cancer.

Inhibitory Effects of Bee Venom on Growth of A549 Lung Cancer Cells via Induction of Death Receptors

  • Jang, Dong Min;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.30 no.1
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    • pp.57-70
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    • 2013
  • This study was to investigated the effects of the bee venom on inhibition of cell growth via upregulation of death receptor expression in the A549 human lung cancer cells. Bee venom(1-5 ${\mu}g$/ml) inhibited the growth of A549 lung cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of TNFR1, Fas, death receptors(DR) 3, 4 and 6 was increased in the cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, -9 and Bax was concomitantly increased, but the expression of Bcl-2, NF-${\kappa}B$ were inhibited by treatment with bee venom in A549 cells. Moreover, deletion of DR3, DR4 by small interfering RNA significantly reversed bee venom-induced cell growth inhibitory effect, whereas Apo3L strengthened anti-proliferative effect of bee venom through enhancement of DR3 expression. These results suggest that bee venom should exert anti-tumor effect through induction of apoptotic cell death in lung cancer cells via enhancement of death receptor expression, and that bee venom could be a promising agent for preventing and treating lung cancer.

Mitochondrial Genome Microsatellite Instability and Copy Number Alteration in Lung Carcinomas

  • Dai, Ji-Gang;Zhang, Zai-Yong;Liu, Quan-Xing;Min, Jia-Xin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2393-2399
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    • 2013
  • Objective: Mitochondrial DNA (mtDNA) is considered a hotspot of mutations in various tumors. However, the relationship between microsatellite instability (MSI) and mtDNA copy number alterations in lung cancer has yet to be fully clarifieds. In the current study, we investigated the copy number and MSI of mitochondrial genome in lung carcinomas, as well as their significance for cancer development. Methods: The copy number and MSI of mtDNA in 37 matched lung carcinoma/adjacent histological normal lung tissue samples were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) assays for sequence variation, followed by sequence analysis and fluorogenic 5'-nuclease real-time PCR. Student's t test and linear regression analyses were employed to analyze the association between mtDNA copy number alterations and mitochondrial MSI (mtMSI). Results: The mean copy number of mtDNA in lung carcinoma tissue samples was significantly lower than that of the adjacent histologically normal lung tissue samples (p<0.001). mtMSI was detected in 32.4% (12/37) of lung carcinoma samples. The average copy number of mtDNA in lung carcinoma samples containing mtMSI was significantly lower than that in the other lung carcinoma samples (P<0.05). Conclusions: Results suggest that mtMSI may be an early and important event in the progression of lung carcinogenesis, particularly in association with variation in mtDNA copy number.