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Pterostilbene Sensitizes Cisplatin-Resistant Human Bladder Cancer Cells with Oncogenic HRAS.
Chen, Yi-Ting; Huang, Zi-Yi; Tang, Han-Hsuan; Kuo, Wan-Ting; Wu, Shan-Ying; Lan, Sheng-Hui; Chang, Kai-Hsun; Lin, Pin-Lun; Lee, Ming-Fen; Cheng, Hung-Chi; Liu, Hsiao-Sheng; Huang, Chi-Ying F; Huang, Guan-Cheng; Su, Chun-Li.
Affiliation
  • Chen YT; Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan.
  • Huang ZY; Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan.
  • Tang HH; Graduate Program of Nutrition Science, School of Life Science, National Taiwan Normal University, Taipei 106, Taiwan.
  • Kuo WT; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
  • Wu SY; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
  • Lan SH; Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
  • Chang KH; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
  • Lin PL; Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan.
  • Lee MF; Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan.
  • Cheng HC; Graduate Program of Nutrition Science, School of Life Science, National Taiwan Normal University, Taipei 106, Taiwan.
  • Liu HS; Department of Human Development and Family Studies, National Taiwan Normal University, Taipei 106, Taiwan.
  • Huang CF; Department of Nutrition, China Medical University, Taichung 404, Taiwan.
  • Huang GC; Department of Nutrition and Health Sciences, Chang Jung Christian University, Tainan 711, Taiwan.
  • Su CL; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Cancers (Basel) ; 12(10)2020 Oct 06.
Article in En | MEDLINE | ID: mdl-33036162
Analysis of various public databases revealed that HRAS gene mutation frequency and mRNA expression are higher in bladder urothelial carcinoma. Further analysis revealed the roles of oncogenic HRAS, autophagy, and cell senescence signaling in bladder cancer cells sensitized to the anticancer drug cisplatin using the phytochemical pterostilbene. A T24 cell line with the oncogenic HRAS was chosen for further experiments. Indeed, coadministration of pterostilbene increased stronger cytotoxicity on T24 cells compared to HRAS wild-type E7 cells, which was paralleled by neither elevated apoptosis nor induced cell cycle arrest, but rather a marked elevation of autophagy and cell senescence in T24 cells. Pterostilbene-induced autophagy in T24 cells was paralleled by inhibition of class I PI3K/mTOR/p70S6K as well as activation of MEK/ERK (a RAS target) and class III PI3K pathways. Pterostilbene-induced cell senescence on T24 cells was paralleled by increased pan-RAS and decreased phospho-RB expression. Coadministration of PI3K class III inhibitor 3-methyladenine or MEK inhibitor U0126 suppressed pterostilbene-induced autophagy and reversed pterostilbene-enhanced cytotoxicity, but did not affect pterostilbene-elevated cell senescence in T24 cells. Animal study data confirmed that pterostilbene enhanced cytotoxicity of cisplatin plus gemcitabine. These results suggest a therapeutic application of pterostilbene in cisplatin-resistant bladder cancer with oncogenic HRAS.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cancers (Basel) Year: 2020 Document type: Article Affiliation country: Taiwan Country of publication: Switzerland

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cancers (Basel) Year: 2020 Document type: Article Affiliation country: Taiwan Country of publication: Switzerland