Three components of cigarette smoke altered the growth and apoptosis of metastatic colon cancer cells via inducing the synthesis of reactive oxygen species and endoplasmic reticulum stress

Abstract

Cigarette smoke (CS) is a well-known risk factor for carcinogenesis and has been found to be related to the occurrence and development of colon cancer. In this study, the effect of formaldehyde (FA), benzene (Bz), and isoprene (IP), which are included in main components of CS, on cell viability and apoptosis of SW620 colorectal cancer cells was examined to identify the connection between CS components and colon cancer. In cell viability assay, FA, Bz, and IP decreased cell viability of SW620 cells in a dose dependent manner. In Western blot assay, the protein expression of cell cycle related genes, cyclin D1 & E1, was decreased by FA, Bz, and IP, which corresponded to their inhibitory effect on cell viability. In addition, FA, Bz, and IP increased the protein expression of pro-apoptotic genes, C/EBP homologous protein (CHOP) and Box, and reduced the protein expression of anti-apoptotic gene, Bcl-2. In reactive oxygen species (ROS) assay using dichlorofluorescin diacetate (DCFH-DA), FA, Bz, and IP increased the ROS production in SW620 cells. In the measurement of apoptotic cells, the numbers of apoptotic cells were increased by the treatment of FA, Bz, and IF. As CHOP is an endoplasmic reticulum (ER)-stress related apoptosis marker of which production is induced by ROS, it was considered that these CS components induce apoptosis of SW620 cells by increasing ROS synthesis and ER-stress. Taken together, these results showed that CS components, i.e., FA, Bz, and IF, inhibited the cell viability of SW620 cells by down-regulating the protein expression of cyclin D1 & E1 and induced apoptosis of SW620 cells by increasing ROS production and simultaneously activating ER-stress. (C) 2016 Elsevier B.V. All rights reserved.