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Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity.
Mol Cancer Ther. 2007 Oct; 6(10):2686-95.MC

Abstract

The present study was undertaken to gain insights into the mechanism of cell cycle arrest caused by honokiol, a constituent of oriental herb Magnolia officinalis. The honokiol treatment decreased the viability of PC-3 and LNCaP human prostate cancer cells in a concentration- and time-dependent manner, which correlated with G0-G1 phase cell cycle arrest. The honokiol-mediated cell cycle arrest was associated with a decrease in protein levels of cyclin D1, cyclin-dependent kinase 4 (Cdk4), Cdk6, and/or cyclin E and suppression of complex formation between cyclin D1 and Cdk4 as revealed by immunoprecipitation using anti-cyclin D1 antibody followed by immunoblotting for Cdk4 protein. The honokiol-treated PC-3 and LNCaP cells exhibited a marked decrease in the levels of total and phosphorylated retinoblastoma protein (Rb), which correlated with the suppression of transcriptional activity of E2F1. Exposure of PC-3 and LNCaP cells to honokiol resulted in the induction of p21 (PC-3 and LNCaP) and p53 protein expression (LNCaP). However, small interfering RNA (siRNA)-mediated knockdown of either p21 (PC-3 and LNCaP) or p53 (LNCaP) protein failed to confer any protection against honokiol-induced cell cycle arrest. The honokiol treatment caused the generation of reactive oxygen species (ROS), and the cell cycle arrest caused by honokiol was partially but significantly attenuated in the presence of antioxidant N-acetylcysteine. In conclusion, the present study reveals that the honokiol-mediated G0-G1 phase cell cycle arrest in human prostate cancer cells is associated with the suppression of protein level/phosphorylation of Rb leading to inhibition of transcriptional activity of E2F1.

Authors+Show Affiliations

Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17938262

Citation

Hahm, Eun-Ryeong, and Shivendra V. Singh. "Honokiol Causes G0-G1 Phase Cell Cycle Arrest in Human Prostate Cancer Cells in Association With Suppression of Retinoblastoma Protein Level/phosphorylation and Inhibition of E2F1 Transcriptional Activity." Molecular Cancer Therapeutics, vol. 6, no. 10, 2007, pp. 2686-95.
Hahm ER, Singh SV. Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity. Mol Cancer Ther. 2007;6(10):2686-95.
Hahm, E. R., & Singh, S. V. (2007). Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity. Molecular Cancer Therapeutics, 6(10), 2686-95.
Hahm ER, Singh SV. Honokiol Causes G0-G1 Phase Cell Cycle Arrest in Human Prostate Cancer Cells in Association With Suppression of Retinoblastoma Protein Level/phosphorylation and Inhibition of E2F1 Transcriptional Activity. Mol Cancer Ther. 2007;6(10):2686-95. PubMed PMID: 17938262.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity. AU - Hahm,Eun-Ryeong, AU - Singh,Shivendra V, PY - 2007/10/17/pubmed PY - 2008/2/8/medline PY - 2007/10/17/entrez SP - 2686 EP - 95 JF - Molecular cancer therapeutics JO - Mol Cancer Ther VL - 6 IS - 10 N2 - The present study was undertaken to gain insights into the mechanism of cell cycle arrest caused by honokiol, a constituent of oriental herb Magnolia officinalis. The honokiol treatment decreased the viability of PC-3 and LNCaP human prostate cancer cells in a concentration- and time-dependent manner, which correlated with G0-G1 phase cell cycle arrest. The honokiol-mediated cell cycle arrest was associated with a decrease in protein levels of cyclin D1, cyclin-dependent kinase 4 (Cdk4), Cdk6, and/or cyclin E and suppression of complex formation between cyclin D1 and Cdk4 as revealed by immunoprecipitation using anti-cyclin D1 antibody followed by immunoblotting for Cdk4 protein. The honokiol-treated PC-3 and LNCaP cells exhibited a marked decrease in the levels of total and phosphorylated retinoblastoma protein (Rb), which correlated with the suppression of transcriptional activity of E2F1. Exposure of PC-3 and LNCaP cells to honokiol resulted in the induction of p21 (PC-3 and LNCaP) and p53 protein expression (LNCaP). However, small interfering RNA (siRNA)-mediated knockdown of either p21 (PC-3 and LNCaP) or p53 (LNCaP) protein failed to confer any protection against honokiol-induced cell cycle arrest. The honokiol treatment caused the generation of reactive oxygen species (ROS), and the cell cycle arrest caused by honokiol was partially but significantly attenuated in the presence of antioxidant N-acetylcysteine. In conclusion, the present study reveals that the honokiol-mediated G0-G1 phase cell cycle arrest in human prostate cancer cells is associated with the suppression of protein level/phosphorylation of Rb leading to inhibition of transcriptional activity of E2F1. SN - 1535-7163 UR - https://www.unboundmedicine.com/medline/citation/17938262/Honokiol_causes_G0_G1_phase_cell_cycle_arrest_in_human_prostate_cancer_cells_in_association_with_suppression_of_retinoblastoma_protein_level/phosphorylation_and_inhibition_of_E2F1_transcriptional_activity_ L2 - http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17938262 DB - PRIME DP - Unbound Medicine ER -