Salicylic Acid Attenuated Actinomycin D Induced Cell Apoptosis in Human Non-Small Cell Lung Carcinoma NCI-H460 Cells

• Main Authors: Ya-Feng Wu, 吳雅鳳
• Other Authors: Chih-Chung Chou
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/4998hg

碩士 === 輔英科技大學 === 生物技術系碩士班 === 98 === Actinomycin D is an antineoplastic antibiotic derived from Streptomyces parvullus that is used for its antineoplastic properties in the treatment of various malignant neoplasms including solid tumors and sarcomas. As a transcriptional inhibitor to inhibit DNA dependent RNA polymerases activity and block mRNA biosynthesis, actinomycin D is a cytotoxic inducer of apoptosis against on tumor cells and inhibits the cellular proliferation in a non-specific pathway. Increase in COX expression has previously been found to be associated with various cancers generation. Inhibition of COX activity by nonsteroidal anti-inflammatory drugs (NSAIDs) such as salicylic acid showed to be effective in reducing metastasis the risk of some cancers. To declare the regulation mechanisms of actinomycin D on apoptosis and COX signaling pathway, human lung carcinoma NCI-H460 cells were treated with salicylic acid offer actinomycin D treated for 3 days. We found that less apoptotic cells were noted in actinomycin D-treated cells in the presence of salicylic acid in a dose- and time-dependent manner from 12 to 72hr. N-acetyl cysteine, a reactive oxygen species inhibitor, Ibuprofen (COX inhibitor), PDTC (NF-κB inhibitor) and PD98059 (ERK inhibitor) failed to diminish actinomycin D induced cytotoxic in NCI-H460 cells. These results suggest that salicylic acid attenuated actinomycin D induced cytotoxic effects seems to be different from inhibition of reactive oxygen species, COX, NF-κB and ERK. The salicylic acid does not restare the cell cycle, indicating that salicylic acid reduced actinomycin D induced cytotoxicity and cell cycle regulation seems irrelevant. In summary, we found salicylic acid reduced apoptosis induced by actinomycin D throughing the activation of Bcl-2 protein.