In this study, the apoptotic effects of the actin disruption agent, latrunculin B(LB) have been investigated on p53 deficient chronic myeloid leukemia cell line K562. A dose-dependent decrease in K562 cell proliferation was observed after LB treatment with maximum decrease in cell proliferation being at 1.5μM where the percent inhibition was 66.53%. F-actin stained with TRITC-phalloidin was shown as a peripheral ring or appeared diffusely distributed throughout the cytoplasm in untreated cells, this actin ring was decreased following LB treatment, and even large focal actin aggregates were formed. Treatment of K562 with LB(1.5μM) generated ROS substantially. LB activated expression in a dose-dependent manner. Therefore it can be concluded that LB, depolymerising agent of actin, induces apoptosis by producing ROS and up-regulating NF-kB and COX-2 activation.

Gemcitabine (Gemzar, 2,2-difluorodeoxycytidine, or dFdC) is an analog of cytosine arabinoside with anti-tumor activity in a few human cancers (lung, ovary, pancreatic and breast cancers). However, the mechanism of apoptosis by this compound in carcinoma has not been fully elucidated. In the present study, we investigated that gemcitabine alone and combination with cisplatin or 5-FU are cancer toxicity using lung cancer cell line A549 by MTT, FACS analysis, and Western blot assay. Also, to confirm enhanced antitumor activity in vivo using an xenograft tumor model. The MTT assay showed higher cytotoxic effect in combination with gemcitabine-cisplatin or gemcitabine-5-FU than gemcitabine alone. FACS analysis showed that gemcitabine-cisplatin combination increased hypodiploid DNA to 70.84 %. The induction of apoptosis showed more increase in combination with gemcitabine-cisplatin or gemcitabine-5-FU than gemcitabine alone. The Western results showed higher expression of p53 and p21WAF/CIP1 protein in combination treatment with gemcitabine-cisplatin or gemcitabine-5-FU than gemcitabine treatment alone. But, Bcl-2 protein expression decreased. In vivo experiments showed that more decreased tumor size and more increased survival rate on combination with gemcitabine- cisplatin or gemcitabine-5-FU combination than gemcitabine alone. In conclusion, this study suggests that gemcitabine combined with cisplatin or 5-FU are the synergistic effect of anticancer therapy on lung cancer.

This study assessed the characteristics of emission and cell toxicology of Methylethylketone(MEK) in ambient air of industrial area. MEK is produced by the oxidation of sec-butyl alcohol and used as the solvent for making ink, printing, coating of film, bonding material and drug extraction. The MEK concentrations in the ambient-air of industrial area in Gimhae City was detected in the range of 25.4～1,580 ㎍/㎥ with an average 297.4 ㎍/㎥. The concentration of MEK showed a descending tendency from April to August followed by its increased tendency since then. The effects of MEK on the human lung cancer A549 cells was examined by the generation of Reactive Oxygen Species(ROS) and cytotoxicity. The range of MEK concentration detected in the area induced ROS generation affecting the oxidation state with a little effects on the viability of the cells.

Endocrine disrupting compounds (EDC's) are chemicals that either mimic endogenous hormones interfering with pharmacokinetics or act by other mechanisms. Some endocrine disrupters were reported to be chemical substances that cause apoptosis in cells. A number of reports have indicated that 1,3-DCP, one of the EDC's may act as an endocrine disrupter and also has possible carcinogenic effects. 1,3-DCP, present in commercial protein hydrolysates used for human nutrition, are genotoxic and 1,3-dichloro-2-propanol induced tumors in rats. In the present study, it was investigated whether 1,3-DCP induces ROS generation and apotosis in A549 adenocarcinoma cells. Here we show that 1,3-DCP inhibits the growth of lung cancer cell lines and generates reactive oxygen species (ROS), a major cause of DNA damage and genetic instability. It was investigated that 1,3-DCP increases G1 phase cells after 12 hours, thereafter abruptly draws A549 cells to G0 state after 24 hours by flow cytometric analysis. 1,3-DCP induces p53 and p21Cip1/WAF1 activation time- and dose-dependently by 24 hours, while the level p21Cip1/WAF1 was decreased after 48 hours. These results suggest that 1,3-DCP, an EDC's generates ROS and regulates genes involved with cell cycle and apoptosis.