Jia-Ching Wu1, Fang-Zong Wang2, Mei-Ling Tsai2, Chih-Yu Lo3, Vladimir Badmaev4, Chi-Tang Ho5, Ying-Jan Wang1,6,7, Min-Hsiung Pan7,8,9. 1. Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, Taiwan. 2. Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung, Taiwan. 3. Department of Food Science, National Chiayi University, Chiayi, Taiwan. 4. American Medical Holdings Inc, New York, NY, USA. 5. Department of Food Science, Rutgers University, New Brunswick, NJ, USA. 6. Department of Biomedical Informatics, Asia University, Taichung, Taiwan. 7. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan. 8. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan. 9. Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
Abstract
SCOPE: Selenium (Se)-conjugated compounds have been established as anti-carcinogenic compounds. The use of chemicals as cancer chemotherapeutic agents to induce programmed cell death (PCD) involves genetic and epigenetic modifications. In this study, we investigated the underlying molecular mechanisms of Se-allylselenocysteine (ASC)-induced PCD and protocadherin 17 (PCDH17) expression in HT-29 cells. METHODS AND RESULTS: Cell viability analysis indicated that the ability of ASC to induce cancer cell death was greater than that of Se-methylselenocysteine in colorectal cancer cells. ASC also decreased global DNA methylation levels via downregulation of DNA methyltransferase 1 expression. The autophagic cell death is the cause in ASC-induced cytotoxicity that was inhibited by pretreatment with autophagy inhibitor. At the molecular level, ASC induced PCDH17 expression through decreased PCDH17 promoter hypermethylation. PCDH17 is also an important role in ASC-induced autophagy by HT-29 transfected with PCDH17 shRNA or expression plasmid. Our western blot analysis showed that ASC significantly induced autophagy via the AMPK/mTOR pathway that was also regulated PCDH17 expression. Additionally, we used the HT-29 tumor xenograft models to confirm the ability of ASC inhibited tumor growth. CONCLUSION: These results reveal that ASC is an effective inducer of autophagy through regulating the AMPK/mTOR and PCDH17 expression via epigenetic modification.
SCOPE: Selenium (Se)-conjugated compounds have been established as anti-carcinogenic compounds. The use of chemicals as cancer chemotherapeutic agents to induce programmed cell death (PCD) involves genetic and epigenetic modifications. In this study, we investigated the underlying molecular mechanisms of Se-allylselenocysteine (ASC)-induced PCD and protocadherin 17 (PCDH17) expression in HT-29 cells. METHODS AND RESULTS: Cell viability analysis indicated that the ability of ASC to induce cancer cell death was greater than that of Se-methylselenocysteine in colorectal cancer cells. ASC also decreased global DNA methylation levels via downregulation of DNA methyltransferase 1 expression. The autophagic cell death is the cause in ASC-induced cytotoxicity that was inhibited by pretreatment with autophagy inhibitor. At the molecular level, ASC induced PCDH17 expression through decreased PCDH17 promoter hypermethylation. PCDH17 is also an important role in ASC-induced autophagy by HT-29 transfected with PCDH17 shRNA or expression plasmid. Our western blot analysis showed that ASC significantly induced autophagy via the AMPK/mTOR pathway that was also regulated PCDH17 expression. Additionally, we used the HT-29 tumor xenograft models to confirm the ability of ASC inhibited tumor growth. CONCLUSION: These results reveal that ASC is an effective inducer of autophagy through regulating the AMPK/mTOR and PCDH17 expression via epigenetic modification.
Authors: Victoria Kaupp; Kinga G Blecharz-Lang; Christina Dilling; Patrick Meybohm; Malgorzata Burek Journal: Neural Regen Res Date: 2023-01 Impact factor: 6.058