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Synergistic Impact of Xanthorrhizol and d-δ-Tocotrienol on the Proliferation of Murine B16 Melanoma Cells and Human DU145 Prostate Carcinoma Cells.
Chan, Darren; Meister, Maureen L; Madhani, Chappell R; Elfakhani, Manal; Yount, Sophie T; Ji, Xiangming; Feresin, Rafaela G; Wanders, Desiree; Mo, Huanbiao.
Afiliación
  • Chan D; Department of Nutrition, Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, Georgia, USA.
  • Meister ML; Department of Nutrition, Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, Georgia, USA.
  • Madhani CR; Department of Nutrition, Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, Georgia, USA.
  • Elfakhani M; Department of Nutrition, Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, Georgia, USA.
  • Yount ST; Department of Chemistry, Georgia State University, Atlanta, Georgia, USA.
  • Ji X; Department of Nutrition, Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, Georgia, USA.
  • Feresin RG; Department of Nutrition, Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, Georgia, USA.
  • Wanders D; Department of Nutrition, Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, Georgia, USA.
  • Mo H; Department of Nutrition, Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta, Georgia, USA.
Nutr Cancer ; 73(9): 1746-1757, 2021.
Article en En | MEDLINE | ID: mdl-32811212
Isoprenoids suppress the mevalonate pathway that provides prenyl groups for the posttranslational modification of growth-regulating proteins. We hypothesize that xanthorrhizol and d-δ-tocotrienol synergistically suppress the growth of murine B16 melanoma and human DU145 prostate carcinoma cells. Xanthorrhizol (0-200 µmol/L; half maximal inhibitory concentration [IC50] = 65 µmol/L) and d-δ-tocotrienol (0-40 µmol/L; IC50 = 20 µmol/L) each induced a concentration-dependent suppression of the proliferation of B16 cells and concurrent cell cycle arrest at the G1 phase. A blend of 16.25 µmol/L xanthorrhizol and 10 µmol/L d-δ-tocotrienol suppressed B16 cell proliferation by 69%, an impact greater than the sum of those induced by xanthorrhizol (15%) and d-δ-tocotrienol (12%) individually. The blend cumulatively reduced the levels of cyclin-dependent kinase four and cyclin D1, key regulators of cell cycle progression at the G1 phase. The expression of RAS and extracellular signal-regulated kinase (ERK1/2) in the proliferation-stimulating RAS-RAF-MEK-ERK pathway was downregulated by the blend. Xanthorrhizol also induced a concentration-dependent suppression of the proliferation of DU145 cells with concomitant morphological changes. Isobologram confirmed the synergistic effect of xanthorrhizol and d-δ-tocotrienol on DU145 cell proliferation with combination index values ranging 0.61-0.94. Novel combinations of isoprenoids with synergistic actions may offer effective approaches in cancer prevention and therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Melanoma Experimental / Carcinoma Límite: Animals / Humans / Male Idioma: En Revista: Nutr Cancer Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Melanoma Experimental / Carcinoma Límite: Animals / Humans / Male Idioma: En Revista: Nutr Cancer Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos