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PEITC induces G1 cell cycle arrest on HT-29 cells through the activation of p38 MAPK signaling pathway
Ka Lung Cheung1, Tin Oo Khor, Siwang Yu
1Graduate Program in Pharmaceutical Science, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.
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.
Insights
Phenethyl isothiocyanate (PEITC) from cruciferous vegetables induces G1 cell cycle arrest in colon cancer cells. This occurs via the p38 MAPK pathway, down-regulating cyclins and pRb.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Phenethyl isothiocyanate (PEITC) is a compound found in cruciferous vegetables.
- PEITC has demonstrated the ability to induce apoptosis in cancer cells, particularly through the MAPK pathway.
Purpose of the Study:
- To investigate the effects of PEITC on cell cycle regulation in HT-29 colon cancer cells.
- To elucidate the specific molecular mechanisms underlying PEITC's impact on cell cycle progression.
Main Methods:
- Flow cytometry was employed to analyze cell cycle distribution.
- Western blot analysis was used to assess protein expression levels, including cyclins and pRb.
- Specific inhibitors were utilized to probe the role of the p38 MAPK pathway.
Main Results:
- PEITC treatment resulted in a significant G1 cell cycle arrest in HT-29 cells.
- The cell cycle arrest was dependent on the activation of the p38 MAPK pathway.
- PEITC caused a dose-dependent down-regulation of cyclins A, D, E, and pRb protein expression.
Conclusions:
- PEITC effectively arrests HT-29 colon cancer cells in the G1 phase.
- This G1 arrest is mediated by the activation of the p38 MAPK signaling pathway.
- PEITC exerts its cell cycle inhibitory effects through the down-regulation of key cell cycle regulatory proteins, including cyclins.
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