Synergistic Impact of Xanthorrhizol and d-δ-Tocotrienol on the Proliferation of Murine B16 Melanoma Cells and Human DU145 Prostate Carcinoma Cells. (18th August 2021)

• Record Type: Journal Article
• Authors: Chan, Darren; Meister, Maureen L.; Madhani, Chappell R.; Elfakhani, Manal; Yount, Sophie T.; Ji, Xiangming; Feresin, Rafaela G.; Wanders, Desiree; Mo, Huanbiao
• Is Part Of: Nutrition and cancer. Volume 73:Number 9(2021)
• Page Start: 1746
• Page End: 1757
• Publication Date: 2021-08-18
• Subjects: Cancer -- Periodicals; Nutrition -- Periodicals; Cancer; Nutrition; Periodicals; 616.9940654
• DOI: 10.1080/01635581.2020.1807573
• Languages: English
• ISSNs: 0163-5581

Abstract

Abstract: 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.