• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4893-4898
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• 2016

Objective: To investigate the impact of a Croton tiglium extract on cellular proliferation and apoptosis in a non-small cell lung cancer cell line (A549) in vitro. Methods: A Croton tiglium seed methanol extract was prepare and assessed for effects on A549 cells regarding cellular proliferation, apoptotic rates, and expression of apoptosis related genes and proteins using real-time PCR and immunofluorescence. Results: The tested Croton tiglium extract inhibited A549 cell proliferation in a dose- and time-dependent manner, with significant elevation of apoptotic indexes at various concentrations after 24 h. In addition, rates in both early and late stages were higher in treated than untreated groups, the $100{\mu}g/ml$ dose causing the highest levels of apoptosis. RT-PCR showed that A549 cells treated with $100{\mu}g/ml$ Croton tiglium extract for 24 h has markedly higher Bax mRNA expression levels and obviously lower Bcl-2 expression levels than controls, equivalent results being observed for proteins by immunofluorescence. However, the mRNA expression levels of Fas and caspase-8 were not significantly altered. Conclusion: A Croton tiglium extract can inhibit proliferation of A549 cells and promote apoptosis though Bax/Bcl-2 pathways.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.6
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• pp.816-822
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• 2015

The objective of this study was to evaluate the anticancer effects of gamma-irradiated apigenin against various human cancer cells. Structural changes were analyzed by high pressure liquid chromatography. Gamma-irradiated apigenin showed a new peak distinguished from the main peak of apigenin (non-irradiated). Cytotoxic effects in human normal cells (HS68) were not observed upon gamma-irradiated and non-irradiated apigenin treatment. However, gamma-irradiated apigenin treatment significantly increased cytotoxicity against non-small lung cancer cells. For apoptosis induction activity tested by Annexin V/PI staining, gamma-irradiated apigenin showed a stronger effect than non-irradiated apigenin, and the level of reactive oxygen species was apparently elevated by gamma-irradiated apigenin treatment. These results suggest that gamma irradiation could be an effective method for development of a new physiological compound from an original compound by inducing structural changes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5883-5887
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• 2015

Despite recent advances in therapeutic strategies for lung cancer, mortality still is increasing. In the present study, we investigated the anti-cancer effects of KMU-193, 2-(4-Ethoxy-phenyl)-N-{5-[2-fluoro-4-(4-methylpiperazine-1-carbonyl)-phenylamino]-1H-indazol-3-yl}-acetamide in a human non-small cell lung cancer cell line A549. KMU-193 strongly inhibited the proliferation of A549 cells, but it did not have anti-proliferative effect in other types of cancer cell lines. KMU-193 further induced apoptosis in association with activation of caspase-3 and cleavage of PLC-${\gamma}1$. However, KMU-193 had no apoptotic effect in untransformed cells such as TMCK-1 and BEAS-2B. Interestingly, pretreatment with z-VAD-fmk, a pan-caspase inhibitor, strongly abrogated KMU-193-induced apoptosis. KMU-193 treatment enhanced the expression levels of p53 and PUMA. Importantly, p53 siRNA transfection attenuated KMU-193-induced apoptosis. Collectively, these results for the first time demonstrate that KMU-193 has strong apoptotic effects on A549 cells and these are largely mediated through caspase-3- and p53-dependent pathways.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.244.1-244.1
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• 2002

Cyclooxygenase-2 ( COX-2 ) is an inducible enzyme which produces prostanoids by various stimuli. Overexpression of COX-2 in many tumor types indicates its association with tumor progression, which has been a promising target for chemoprevention and chemomodulation. We studied conc- and time-dependency of COX-2 inhibition, growth inhibition, and cell cycle arrest induced by celecoxib, a selective COX-2 inhibitor, in human non-small cell lung cancer (NSCLC) A549 cells. (omitted)

• Proceedings of the Korean Society of Life Science Conference
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• 2005.09a
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• pp.35-35
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• 2005

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7295-7300
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• 2013

Lung cancer is the most common cause of cancer-related death in the world. The main types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), the latter including squamous cell carcinoma (SCC), adenocarcinoma and large cell carcinoma. NSCLCs account for about 80% of all lung cancer cases. Microcephalin (MCPH1), also called BRIT1 (BRCT-repeat inhibitor of hTERT expression), plays an important role in the maintenance of genomic stability. Recently, several studies have provided evidence that the expression of MCPH1 gene is decreased in several different types of human cancers. We evaluated the expression of protein MCPH1 in 188 lung cancer and 20 normal lung tissues by immunohistochemistry. Positive MCPH1 staining was found in all normal lung samples and only some cancerous tissues. MCPH1-positive cells were significantly lower in lung carcinoma compared with normal tissues. Furthermore, we firstly found that MCPH1 expression in lung adenocarcinoma is higher than its expression in squamous cell carcinoma. Change in MCPH1 protein expression may be associated with lung tumorigenesis and may be a useful biomarker for identification of pathological types of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.56 no.4
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• pp.381-392
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• 2004

Arsenic trioxide($As_2O_3$) was introduced into the treatment of refractory or relapsed acute promyelocytic Ieukemia. Some investigators have reported that arsenic trioxide had induced apoptosis in a variety of solid human tumor cell lines, including non-small cell lung cancer. Non-steroidal anti-inflammatory drugs(NSAIDs) are powerful chemopreventive agents for gastrointestinal cancers and the growth of established tumors are reduced by inducing apoptosis. It's also reported that NSAIDs enhanced tumor response to chemotherapeutic drugs or radiation. In this study, we aimed to determine whether combination of arsenic trioxide with sulindac augmented its apoptotic potential in NCI-H157 human lung cancer cells. The human lung cancer cell line NCI-H157 was treated with arsenic trioxide and sulindac. Cell viability was measured by the MTT assay. Apoptosis was measured by nuclear staining and flow cytometric analysis. The catalytic activity of the caspase families were measured by the fluorogenic cleavage of biosubstrates. The western blotting were also performed to define the mechanical basis of apoptosis. Combination treatment of arsenic trioxide and sulindac decreased the viability of NCI-H157 human lung cancer cells in a dose-dependent manner. The catalytic activity of caspase-3, 8 and 9 proteases were increased after combination treatment. Consistently PARP was cleaved from 116kDa to 85kDa fragments, and the expression of ICAD was decreased by time-dependent manner. Also combination treatment increased the expression of Fas and Fas/L. Combination therapy of arsenic trioxide with sulindac augments cell death and induces apoptosis via the activation of caspase cascade in NCI-H157 human lung carcinoma cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2425-2430
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• 2015

Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. EHZ2 is involved in drug resistance and is overexpressed in drug-resistant cancer cell lines. In this study, we investigated the effects of EHZ2 on cisplatin -resistance in A549/DDP and AGS/DDP cells. EHZ2 mRNA and protein were found to be significantly overexpressed in A549/DDP and AGS/DDP cells, compared to parental cells. EHZ2 siRNA successfully silenced EHZ2 mRNA and protein expression. Proliferation was inhibited and drug resistance to cisplatin was improved. Flow cytometry showed that silencing of EHZ2 arrested A549/DDP and AGS/DDP cells in the G0/G1 phase, increasing apoptosis, rh-123 fluorescence intensity and caspase-3/8 activities. Silencing of EHZ2 also significantly reduced the mRNA and protein expression levels of cyclin D1 and MDR1,while up-regulating p15, p21, p27 and miR-218 in A549/DPP cells. Furthermore, silencing of EHZ2 also significantly increased the expression level of tumor suppressor factor miR-218. We also found down-regulating EHZ2 expression increased methylation in A549/DDP and AGS/DDP cells. This study demonstrates that drug resistance can be effectively reversed in human cisplatin-resistant lung and gastric cancer cells through delivery of siRNAs targeting EHZ2.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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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 Life Science
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• v.33 no.9
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• pp.713-723
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• 2023

Lung cancer is a type of cancer that has the highest mortality rate. It is mainly classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Chemotherapy is used to treat lung cancer, but long-term treatment causes side effects and drug resistances. Curcumin is a bright yellow polyphenol extracted from the root of turmeric. It has biological activities, such as anti-oxidant, anti-cancer, and anti-inflammatory effects. In this study, we observed differential cell death in human lung cancer cells. Based on the results, curcumin at 10, 30, and 50 μM exhibited a dose-dependent inhibition on the cell survival of several lung cancer cells, with minor differential phenotypes. In addition, apoptosis, autophagy, and reactive oxygen species (ROS) regeneration were observed through flow cytometry. Curcumin dose-dependently increased these phenotypes in A549 (NSCLC) and DMS53 (SCLC), which were restored by corresponding inhibitors. Western blotting was performed to measure the level of expression of apoptosis- and autophagy-related proteins. The results indicate that Bax, PARP, pro-caspase-3, and Bcl-2 were dose-dependently regulated by curcumin, with seemingly higher Bax/Bcl-2 ratios in DMS53. In addition, autophagic proteins, p-AKT, p62, and LC3B, were dose-dependently regulated by curcumin. ROS inhibition by diphenyleneiodonium reduced the induction of apoptosis and autophagy generated by curcumin. Taken together, it is suggested that curcumin induces apoptosis and autophagy via ROS generation, leading to cell death, with minor differences between human lung cancer cells.