Toshiyuki Tsunoda1, Shuhei Ishikura1, Keiko Doi1, Hiroshi Matsuzaki2, Yuri Iwaihara2, Senji Shirasawa3. 1. Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka, Japan. 2. Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. 3. Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka, Japan sshirasa@fukuoka-u.ac.jp.
Abstract
BACKGROUND: We have previously reported the crucial roles of oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) in inhibiting apoptosis and disrupting cell polarity via the regulation of phosphodiesterase 4 (PDE4) expression in human colorectal cancer HCT116 cells in three-dimensional cultures (3DC). Herein we evaluated the effects of resveratrol, a PDE4 inhibitor, on the luminal cavity formation and the induction of apoptosis in HCT116 cells. MATERIALS AND METHODS: Apoptosis was detected by immunofluorescence using confocal laser scanning microscopy with an antibody against cleaved caspase-3 in HCT116 cells treated with or without resveratrol in a two-dimensional culture (2DC) or 3DC. RESULTS: Resveratrol did not induce apoptosis of HCT116 cells in 2DC, whereas the number of apoptotic HCT116 cells increased after resveratrol treatment in 3DC, leading to formation of a luminal cavity. CONCLUSION: Resveratrol induced apoptosis of HCT116 cells in 3DC, resulting in the formation of a luminal cavity, probably by inhibiting PDE4 activity. Copyright
BACKGROUND: We have previously reported the crucial roles of oncogenic Kirsten ratsarcoma viral oncogene homolog (KRAS) in inhibiting apoptosis and disrupting cell polarity via the regulation of phosphodiesterase 4 (PDE4) expression in humancolorectal cancer HCT116 cells in three-dimensional cultures (3DC). Herein we evaluated the effects of resveratrol, a PDE4 inhibitor, on the luminal cavity formation and the induction of apoptosis in HCT116 cells. MATERIALS AND METHODS: Apoptosis was detected by immunofluorescence using confocal laser scanning microscopy with an antibody against cleaved caspase-3 in HCT116 cells treated with or without resveratrol in a two-dimensional culture (2DC) or 3DC. RESULTS:Resveratrol did not induce apoptosis of HCT116 cells in 2DC, whereas the number of apoptotic HCT116 cells increased after resveratrol treatment in 3DC, leading to formation of a luminal cavity. CONCLUSION:Resveratrol induced apoptosis of HCT116 cells in 3DC, resulting in the formation of a luminal cavity, probably by inhibiting PDE4 activity. Copyright
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