Abstract
Hydroxyurea is commonly used to treat hematologic disorders and some type of solid tumors, but the mechanism for its therapeutic effect is not clearly known. In this study, we examined the effect of hydroxyurea on rat hepatoma McA-RH7777 cells, specifically, on the role of mitogen-activated protein (MAP) kinase signal transduction pathways and p21(Waf1), p27(Kip1) and p53. Rat hepatoma McA-RH7777 cells treated with hydroxyurea for 7 days, caused the inhibition of cell growth in a dose-dependent manner. But, this growth inhibition was not caused by necrosis or apoptosis but instead was associated with cell senescence-like change as evidenced by senescence associated-beta-galactosidase staining, and cells arrest at G1 phase of cell cycle. Phosphorylation of MAP kinases, such as ERK, JNK, and p38, was found to be decreased after treatment of cells with hydroxyurea. But, the expression of p21(Waf1) was increased, while p27(Kip1) and p53 were not detected in hydroxyurea treated rat hepatoma cells. Hydroxyurea treatment induced G1 arrest and a senescence-like changes in rat hepatoma McA-RH7777 cells may be the likely results of signal disruption of MAP kinases (ERK, JNK, and p38 MAP kinase) and p21(Waf1) over-expression.
Highlights
Hydroxyurea (HU) is a free radical quencher that inhibits a cellular enzyme, ribonucleoside diphosphate reductase and, in so doing, reduces the levels of deoxyribonucleotides (Krakoff et al, 1968)
To learn more about the signaling pathways used by HU and the molecules which are involved in transducing signaling from HU, we investigated whether cell cycle regulators in m itogen-activated protein (MAP) kinase signaling pathways, p21Waf1, p27Kip1 and p53 can play roles in HU effects toward rat hepatoma cell line McA-RH7777
We investigated whether HU induced similar effects on rat hepatoma McA-RH7777 cells
Summary
Hydroxyurea (HU) is a free radical quencher that inhibits a cellular enzyme, ribonucleoside diphosphate reductase and, in so doing, reduces the levels of deoxyribonucleotides (Krakoff et al, 1968). Hydroxyurea treatm ent induced G1 arrest and a senescence-like changes in rat hepatom a M cA-RH7777 cells m ay be the likely results of signal disruption of M AP kinases (ERK, JNK, and p38 M A P kinase) and p21Waf1 over-expression. To learn more about the signaling pathways used by HU and the molecules which are involved in transducing signaling from HU, we investigated whether cell cycle regulators in MAP kinase signaling pathways, p21Waf1, p27Kip1 and p53 can play roles in HU effects toward rat hepatoma cell line McA-RH7777.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
