• Clinical and Experimental Pediatrics
• /
• v.52 no.2
• /
• pp.213-219
• /
• 2009

Purpose:Iron is a critical nutritional element that is essential for a variety of important biological processes, including cell growth and differentiation, electron transfer reactions, and oxygen transport, activation, and detoxification. Iron is also required for neoplastic cell growth due to its catalytic effects on the formation of hydroxyl radicals, suppression of host defense cell activities, and promotion of cancer cell multiplication. Chronic transfusion-dependent patients receiving chemotherapy may have iron overload, which requires iron-chelating therapy. We performed this study to demonstrate whether the iron chelating agent deferoxamine induces apoptosis in Saos-2 osteosarcoma cells, and to investigate the underlying apoptotic mechanism. Methods:To analyze the apoptotic effects of an iron chelator, cultured Saos-2 cells were treated with deferoxamine. We analyzed cell survival by trypan blue and crystal violet analysis, apoptosis by nuclear condensation, DNA fragmentation, and cell cycle analysis, and the expression of apoptotic related proteins by Western immunoblot analysis. Results:Deferoxamine inhibited the growth of Saos-2 cell in a time- and dose-dependent manner. The major mechanism for growth inhibition with the deferoxamine treatment was by the induction of apoptosis, which was supported by nuclear staining, DNA fragmentation analysis, and flow cytometric analysis. Furthermore, bcl-2 expression decreased, while bax, caspase-3, caspase-9, and PARP expression increased in Saos-2 cells treated with deferoxamine. Conclusion:These results demonstrated that the iron chelating agent deferoxamine induced growth inhibition and mitochondrial-dependent apoptosis in osteosarcoma Saos-2 cells, suggesting that iron chelating agents used in controlling neoplastic cell fate can be potentially developed as an adjuvant agent enhancing the anti-tumor effect for the treatment of osteosarcoma.

• Tuberculosis and Respiratory Diseases
• /
• v.51 no.4
• /
• pp.315-324
• /
• 2001

Background : IL-8 is a potent chemotactic cytokine that plays an important role in the host defense mechanism against M. tuberculosis by recruiting inflammatory cells to the site of the infection. Lung epithelial cells, as well as alveolar macrophages are known to produce IL-8 in response to M. tuberculosis. IL-8 gene expression is mainly regulated on the level of transcription by NF-${\kappa}B$. This study investigated whether or not A549 cells produce IL-8 in NF-${\kappa}B$ dependent mechanism in response to macrophages phagocytosing M. tuberculosis. Methods : Peripheral blood monocytes that were obtained from healthy donors were cultured for 24 h with M. tuberculosis and a conditioned medium(CoMTB) was obtained. As a negative control, the conditioned medium without M. tuberculosis (CoMCont) was used. A549 cells were stimulated with M. tuberculosis, CoMCont and CoMTB and the IL-8 concentration in the culture media was measured by ELISA. The CoMTB induced IL-8 mRNA expression in the A549 cells was evaluated using RT-PCR, and CoMTB induced $I{\kappa}B{\alpha}$ degradation was measured using western blot analysis. CoMTB induced nuclear translocation and DNA binding of NF-${\kappa}B$ was also examined using an electrophoretic mobility shift assay(EMSA), and the CoMTB induced NF-${\kappa}B$ dependent IL-8 transcriptional activity was measured using a luciferase reporter gene assay. Results : CoMTB induced IL-8 production by A549 cells($46.8{\pm}4.8\;ng/ml$) was higher than with direct stimulation with M. tuberculosis ($6.8{\pm}2.9\;ng/ml$). CoMTB induced IL-8 mRNA expression increased after 2 h of stimulation and was sustained for 24 h. $I{\kappa}B{\alpha}$ was degraded after 10 min of CoMTB stimulation and reappeared by 60 min. CoMTB stimulated the nuclear translocation and DNA binding of NF-${\kappa}B$. The CoMTB induced NF-${\kappa}B$ dependent IL-8 transcriptional activity($13.6{\pm}4.3$ times control) was higher than either CoMCont($2.0{\pm}0.6$ times control) or M. tuberculosis ($1.4{\pm}0.6$ times control). Conclusion : A conditioned medium of peripheral blood monocytes phagocytosing M. tuberculosis stimulates NF-${\kappa}B$ dependent IL-8 production by the lung epithelial cells.

• Journal of the Korean Geographical Society
• /
• v.38 no.2
• /
• pp.312-323
• /
• 2003

This writer absolutely agrees with the government that regional disequilibrium is severe enough to consider moving the administrative capital. Pursuing this course solely to establish a balanced development, however, is not a convincing enough reason. The capital city is directly related to not only the social and economic situation but, much more importantly, to the domestic political situation as well. In the mid-1970s, the proposal by the Third Republic to move the capital city temporarily was based completely on security reasons. At e time, the then opposition leader Kim, Dae-jung said that establishing a safe distance from the demilitarized zone(DMZ) reflected a typically military decision. His view was that retaining the capital city close to the DMZ would show more consideration for the will of the people to defend their own country. In fact, independent Pakistan moved its capital city from Karachi to Islamabad, situated dose to Kashmir the subject of hot territorial dispute with India. It is regrettable that no consideration has been given to the urgent political situation in the Korean peninsula, which is presently enveloped in a dense nuclear fog. As a person requires health to pursue his/her dream, a country must have security to implement a balanced territorial development. According to current urban theories, the fate of a country depends on its major cities. A negligently guarded capital city runs the risk of becoming hostage and bringing ruin to the whole country. In this vein, North Koreas undoubted main target of attack in the armed communist reunification of Korea is Seoul. For the preservation of our state, therefore, it is only right that Seoul must be shielded to prevent becoming hostage to North Korea. The location of the US Armed Forces to the north of the capital city is based on the judgment that defense of Seoul is of absolute importance. At the same time, regardless of their different standpoints, South and North Korea agree that division of the Korean people into two separate countries is abnormal. Reunification, which so far has defied all predictions, may be realized earlier than anyone expects. The day of reunification seems to be the best day for the relocation of the capital city. Building a proper capital city would take at least twenty years, and a capital city cannot be dragged from one place to another. On the day of a free and democratic reunification, a national agreement will be reached naturally to find a nationally symbolic city as in Brazil or Australia. Even if security does not pose a problem, the governments way of thinking would not greatly contribute to the balanced development of the country. The Chungcheon region, which is earmarked as the new location of the capital city, has been the greatest beneficiary of its proximity to the capital region. Not being a disadvantaged region, locating the capital city there would not help alleviate regional disparity. If it is absolutely necessary to find a candidate region at present, considering security, balanced regional development and post-reunification scenario of the future, Cheolwon area located in the middle of the Korean peninsula may be a plausible choice. Even if the transfer of capital is delayed in consideration of the present political conflict between the South and the North Koreas, there is a definite shortcut to realizing a balanced regional development. It can be found not in the geographical dispersal of the central government, but in the decentralization of power to the provinces. If the government has surplus money to build a new symbolic capital city, it is only right that it should improve, for instance, the quality of drinking water which now everyone eschews, and to help the regional subway authority whose chronic deficit state resoled in a recent disastrous accident. And it is proper to time the transfer of capital city to coincide with that of the reunification of Korea whenever Providence intends.