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  • PEITC induces G1 cell cycle arrest on HT-29 cells through the activation of p38 MAPK signaling pathway.

PEITC induces G1 cell cycle arrest on HT-29 cells through the activation of p38 MAPK signaling pathway.

The AAPS journal (2008-05-14)
Ka Lung Cheung, Tin Oo Khor, Siwang Yu, Ah-Ng Tony Kong
ABSTRACT

Phenethyl isothiocyanate (PEITC), an isothiocyanate abundantly found in cruciferous vegetables have been shown to induce apoptosis through MAPK pathway in prostate and colon cancer cells. In the present study, we investigate the effect of PEITC on cell cycle regulation of HT-29 colon cancer cells. Using flow cytometry and Western blot analyses, we found that PEITC significantly induced G1 cell cycle arrest in HT-29 cells. We showed that the cell cycle arrest was not related to beta-catenin translocation into the nucleus. Interestingly, inhibition of p38 attenuated the cell cycle arrest, suggesting that cell cycle arrest by PEITC was caused by the activation of MAPK pathway. Treatments of PEITC resulted in a dose-dependent down-regulation of cyclins A, D, E and pRb protein expression. The down-regulation can be attributed to the activation of the p38 pathway, since inhibition of its activities by specific inhibitor blocked PEITC's ability to decrease the expression level of cyclins A and D and attenuate cell cycle arrest effect of PEITC. In conclusion, this study shows for the first time that PEITC can arrest HT-29 cells in G1 phase by down-regulation of cyclins through the activation of p38 MAPK signaling pathway.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Phenethyl isothiocyanate, 99%
Sigma-Aldrich
PD 98059, PD 98059, CAS 167869-21-8, is a cell-permeable, selective & reversible inhibitor of MAP Kinase Kinase (MEK). Inhibits MAP Kinase activation and subsequent phosphorylation of MAP Kinase substrates.
Sigma-Aldrich
JNK Inhibitor II, JNK Inhibitor II. SP600125, CAS 129-56-6, is a potent, cell-permeable, selective, and ATP competitive inhibitor of c-Jun N-terminal kinase (JNK; IC₅₀ = 40 nM for JNK-1 & JNK-2 & 90 nM for JNK-3).
Sigma-Aldrich
SB 203580, SB 203580, CAS 152121-47-6, is a highly specific, potent, cell-permeable, selective, reversible, and ATP-competitive inhibitor of p38 MAP kinase (IC₅₀ = 34 nM in vitro, 600 nM in cells).