TY - JOUR
T1 - Sensory acceptable equivalent doses of β-phenylethyl isothiocyanate (PEITC) induce cell cycle arrest and retard the growth of p53 mutated oral cancer in vitro and in vivo
AU - Lam-Ubol, Aroonwan
AU - Fitzgerald, Alison Lea
AU - Ritdej, Arnat
AU - Phonyiam, Tawaree
AU - Zhang, Hui
AU - Myers, Jeffrey N.
AU - Huang, Peng
AU - Trachootham, Dunyaporn
N1 - Funding Information:
Dr Lam-ubol and Dr Trachootham received a research grant from the Dental Innovation Foundation under Royal Patronage, His Majesty the King’s Dental Service Unit. Other conflicts of interest: none.
Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2018/7
Y1 - 2018/7
N2 - High doses of β-phenylethyl isothiocyanate (PEITC), a phytochemical in cruciferous vegetables, are not feasible for consumption due to a strong mouth-tingling effect. This study investigated the anti-cancer effect of PEITC at sensory acceptable doses. In vitro, PEITC was selectively toxic to oral cancer cells (CAL-27, FaDu, SCC4, SCC 9, SCC15, SCC25 and TU138), compared to oral keratinocytes (OKF6/TERT2 and NOK/Si). In vivo, 5 and 10 mg kg-1 PEITC, equivalent to human organoleptically acceptable doses, retarded tumor growth and prolonged the survival of mice bearing p53-mutated oral cancer cells-TU138 xenograft. Mechanistically, PEITC induced ROS accumulation, nuclear translocation of p53 and p21 and G1/S cell cycle arrest in vitro; increased p53 and 8-oxo-dG levels; and decreased Ki-67 intense/mild staining ratios without TUNEL changes in vivo. These findings suggested that the sensory acceptable doses of PEITC selectively induced ROS-mediated cell cycle arrest leading to delayed tumor progression and extended survival. PEITC could be a functional ingredient for oral cancer prevention.
AB - High doses of β-phenylethyl isothiocyanate (PEITC), a phytochemical in cruciferous vegetables, are not feasible for consumption due to a strong mouth-tingling effect. This study investigated the anti-cancer effect of PEITC at sensory acceptable doses. In vitro, PEITC was selectively toxic to oral cancer cells (CAL-27, FaDu, SCC4, SCC 9, SCC15, SCC25 and TU138), compared to oral keratinocytes (OKF6/TERT2 and NOK/Si). In vivo, 5 and 10 mg kg-1 PEITC, equivalent to human organoleptically acceptable doses, retarded tumor growth and prolonged the survival of mice bearing p53-mutated oral cancer cells-TU138 xenograft. Mechanistically, PEITC induced ROS accumulation, nuclear translocation of p53 and p21 and G1/S cell cycle arrest in vitro; increased p53 and 8-oxo-dG levels; and decreased Ki-67 intense/mild staining ratios without TUNEL changes in vivo. These findings suggested that the sensory acceptable doses of PEITC selectively induced ROS-mediated cell cycle arrest leading to delayed tumor progression and extended survival. PEITC could be a functional ingredient for oral cancer prevention.
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U2 - 10.1039/c8fo00865e
DO - 10.1039/c8fo00865e
M3 - Article
C2 - 29923573
AN - SCOPUS:85050534112
SN - 2042-6496
VL - 9
SP - 3640
EP - 3656
JO - Food and Function
JF - Food and Function
IS - 7
ER -