The Effect of MAPK Inhibitors on Arsenic Trioxide-treated Calu-6 Lung Cells in Relation to Cell Death, ROS and GSH Levels

• Published in: Anticancer research Vol. 29; no. 10; pp. 3837 - 3844
• Main Authors: Han, Yong Hwan, Moon, Hwa Jin, You, Bo Ra, Kim, Sung Zoo, Kim, Suhn Hee, Park, Woo Hyun
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.10.2009
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - enzymology; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Allium cepa; Antineoplastic Agents - pharmacology; Arsenicals - pharmacology; Biological and medical sciences; Cell Cycle - drug effects; Cell Growth Processes - drug effects; Cell Line, Tumor; Drug Synergism; Glutathione - metabolism; Humans; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors; Lung Neoplasms - drug therapy; Lung Neoplasms - enzymology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical sciences; Membrane Potential, Mitochondrial - drug effects; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Oxides - pharmacology; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; Protein Kinase Inhibitors - pharmacology; Reactive Oxygen Species - metabolism; Tumors; Enzyme; Transferases; Lung; Mitogen-activated protein kinase; Arsenic trioxide; MAPK; Respiratory system; Calu-6; Cancerology; Treatment; Cell death; ROS; Inhibitor; GSH; Apoptosis
• ISSN: 0250-7005; 1791-7530

Arsenic trioxide (ATO) can regulate many biological functions such as apoptosis and differentiation. We recently demonstrated that ATO-induced apoptosis in Calu-6 lung cancer cells is correlated with glutathione (GSH) content. Here, the effects of ATO and/or mitogen-activated protein kinase (MAPK) inhibitors on Calu-6 cells were investigated in relation to cell growth, cell death, reactive oxygen species (ROS) and GSH levels. Treatment with ATO inhibited the growth of the Calu-6 cells at 72 hours. ATO induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨ m ). While general nonspecific ROS decreased in the ATO-treated Calu-6 cells, the intracellular superoxide anion (O 2 •- ) level including mitochondrial O 2 •- increased. ATO also induced GSH depletion in the Calu-6 cells. The treatment with MAP kinase kinase (MEK), c-Jun N-terminal kinase (JNK) and p38 inhibitors intensified the cell growth inhibition, cell death, MMP (ΔΨ m ) loss, and GSH depletion in the ATO-treated Calu-6 cells. In addition, the JNK and p38 inhibitors significantly increased the ROS levels including O 2 •- in the ATO-treated Calu-6 cells. In conclusion, all the MAPK inhibitors slightly intensify cell death in the ATO-treated Calu-6 cells and the changes of ROS and GSH brought about by ATO and/or MAPK inhibitor treatment partially influence cell growth and death in Calu-6 cells.