Yung-Luen Shih1,2,3, Fang-Ming Hung4, Ching-Hsiao Lee5, Ming-Yang Yeh6, Mei-Hui Lee7, Hsu-Feng Lu8,9, Yung-Liang Chen10, Jia-You Liu11, Jing-Gung Chung12. 1. Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, R.O.C. 2. School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan, R.O.C. 3. School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, R.O.C. 4. Department of Surgical Intensive Care Unit, Far Eastern Memorial Hospital, New Taipei, Taiwan, R.O.C. 5. Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli County, Taiwan, R.O.C. 6. Department of Medical Education and Research, Cheng Hsin General Hospital, Taipei, Taiwan, R.O.C. 7. Department of Genetic Counseling Center, Changhua Christian Hospital, Changhua, Taiwan, R.O.C. 8. Department of Restaurant, Hotel and Institutional Management, Fu-Jen Catholic University, New Taipei City, Taiwan, R.O.C. 9. Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan, R.O.C. 10. Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu, Taiwan, R.O.C. 11. Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan, R.O.C. jgchung@mail.cmu.edu.tw ch1835@chgh.org.tw. 12. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C. jgchung@mail.cmu.edu.tw ch1835@chgh.org.tw.
Abstract
BACKGROUND/AIM: Oral cancer has been reported to be one of the major cancer-related diseases in human populations and the treatment of oral cancer is still unsatisfied. Fisetin, is a flavonoid from plants and has several biological activities such as antioxidant, anti-inflammatory and anticancer function, but its cytotoxicity in human oral cancer cells is unknown. In the present study, we investigated fisetin-induced cytotoxic effects on HSC3 human oral cancer cells in vitro. Materials and Methods/ Results: We used flow cytometric assay to show fisetin induced apoptotic cell death through increased reactive oxygen species and Ca2+, but reduced the mitochondrial membrane potential and increased caspase-8, -9 and -3 activities in HSC3 cells. Furthermore, we also used 4' 6-diamidino-2-phenylindole staining to show that fisetin induced chromatin condensation (apoptotic cell death), and Comet assay to show that fisetin induced DNA damage in HSC3 cells. Western blotting was used to examine the levels of apoptotic-associated protein and results indicated that fisetin increased expression of pro-apoptotic proteins such as B-cell lymphoma 2 (BCL2) antagonist/killer (BAK) and BCL2-associated X (BAX) but reduced that of anti-apoptotic protein such as BCL2 and BCL-x, and increased the cleaved forms of caspase-3, -8 and -9, and cytochrome c, apoptosis-inducing factor (AIF) and endonuclease G (ENDO G) in HSC3 cells. Confocal microscopy showed that fisetin increased the release of cytochrome c, AIF and ENDO G from mitochondria into the cytoplasm. CONCLUSION: Based on these observations, we suggest that fisetin induces apoptotic cell death through endoplasmic reticulum stress- and mitochondria-dependent pathways. Copyright
BACKGROUND/AIM: Oral cancer has been reported to be one of the major cancer-related diseases in human populations and the treatment of oral cancer is still unsatisfied. Fisetin, is a flavonoid from plants and has several biological activities such as antioxidant, anti-inflammatory and anticancer function, but its cytotoxicity in humanoral cancer cells is unknown. In the present study, we investigated fisetin-induced cytotoxic effects on HSC3 human oral cancer cells in vitro. Materials and Methods/ Results: We used flow cytometric assay to show fisetin induced apoptotic cell death through increased reactive oxygen species and Ca2+, but reduced the mitochondrial membrane potential and increased caspase-8, -9 and -3 activities in HSC3 cells. Furthermore, we also used 4' 6-diamidino-2-phenylindole staining to show that fisetin induced chromatin condensation (apoptotic cell death), and Comet assay to show that fisetin induced DNA damage in HSC3 cells. Western blotting was used to examine the levels of apoptotic-associated protein and results indicated that fisetin increased expression of pro-apoptotic proteins such as B-cell lymphoma 2 (BCL2) antagonist/killer (BAK) and BCL2-associated X (BAX) but reduced that of anti-apoptotic protein such as BCL2 and BCL-x, and increased the cleaved forms of caspase-3, -8 and -9, and cytochrome c, apoptosis-inducing factor (AIF) and endonuclease G (ENDO G) in HSC3 cells. Confocal microscopy showed that fisetin increased the release of cytochrome c, AIF and ENDO G from mitochondria into the cytoplasm. CONCLUSION: Based on these observations, we suggest that fisetin induces apoptotic cell death through endoplasmic reticulum stress- and mitochondria-dependent pathways. Copyright
Authors: Daniel R Gomez; Joanne E Zhung; Jennifer Gomez; Kelvin Chan; Abraham J Wu; Suzanne L Wolden; David G Pfister; Ashok Shaha; Jatin P Shah; Dennis H Kraus; Richard J Wong; Nancy Y Lee Journal: Int J Radiat Oncol Biol Phys Date: 2008-08-15 Impact factor: 7.038
Authors: Daniel W Cole; Peter F Svider; Kerolos G Shenouda; Paul B Lee; Nicholas G Yoo; Thomas M McLeod; Sean A Mutchnick; George H Yoo; Randal J Kaufman; Michael U Callaghan; Andrew M Fribley Journal: Exp Cell Res Date: 2019-05-07 Impact factor: 3.905