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Zanthoxyli Fructus induces growth arrest and apoptosis of LNCaP human prostate cancer cells in vitro and in vivo in association with blockade of the AKT and AR signal pathways.
Oncol Rep 2006; 15(6):1581-90OR

Abstract

Zanthoxyli Fructus belongs to the family of oranges and is used as a seasoning in Asian countries including Japan. This study found that a water extract of Zanthoxyli Fructus possessed anti-tumor activity against a wide variety of cancer cells including those from prostate (LNCaP, DU145, PC-3), breast (MCF-7, T47D, MDA-MB231), lung (NCI-H460, -H520), as well as leukemia (HL-60, NB4, Jurkat) in vitro, as measured by the trypan blue exclusion test. Importantly, Zanthoxyli Fructus slowed the proliferation of LNCaP, DU145, and MDA-MB231 cells present as xenografts in BALB/c nude mice without adverse effects. Further studies explored the molecular mechanism by which Zanthoxyli Fructus inhibited the proliferation of androgen-dependent human prostate cancer LNCaP cells because Zanthoxyli Fructus possessed the strongest anti-tumor activity against these cells. Zanthoxyli Fructus blocked androgen receptor (AR) signaling in conjunction with down-regulation of nuclear levels of AR and induced apoptosis of these cells, as measured by the reporter assay, Western blot analysis, and TUNEL assay, respectively. As expected, Zanthoxyli Fructus also decreased the level of the AR-target molecule, prostate-specific antigen in these cells. Furthermore, Zanthoxyli Fructus inhibited AKT kinase and down-regulated levels of cyclin D1 protein, as measured by the AKT kinase assay with GSK-3alpha/beta as a substrate and Western blot analysis, respectively. Taken together, Zanthoxyli Fructus might be useful as an adjunctive therapeutic agent for the treatment of individuals with a variety of cancer types.

Authors+Show Affiliations

Department of Hematology and Respiratory Medicine, Kochi University, Okohcho, Nankoku, Kochi 783-8505, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16685399

Citation

Yang, Yang, et al. "Zanthoxyli Fructus Induces Growth Arrest and Apoptosis of LNCaP Human Prostate Cancer Cells in Vitro and in Vivo in Association With Blockade of the AKT and AR Signal Pathways." Oncology Reports, vol. 15, no. 6, 2006, pp. 1581-90.
Yang Y, Ikezoe T, Takeuchi T, et al. Zanthoxyli Fructus induces growth arrest and apoptosis of LNCaP human prostate cancer cells in vitro and in vivo in association with blockade of the AKT and AR signal pathways. Oncol Rep. 2006;15(6):1581-90.
Yang, Y., Ikezoe, T., Takeuchi, T., Adachi, Y., Ohtsuki, Y., Koeffler, H. P., & Taguchi, H. (2006). Zanthoxyli Fructus induces growth arrest and apoptosis of LNCaP human prostate cancer cells in vitro and in vivo in association with blockade of the AKT and AR signal pathways. Oncology Reports, 15(6), pp. 1581-90.
Yang Y, et al. Zanthoxyli Fructus Induces Growth Arrest and Apoptosis of LNCaP Human Prostate Cancer Cells in Vitro and in Vivo in Association With Blockade of the AKT and AR Signal Pathways. Oncol Rep. 2006;15(6):1581-90. PubMed PMID: 16685399.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Zanthoxyli Fructus induces growth arrest and apoptosis of LNCaP human prostate cancer cells in vitro and in vivo in association with blockade of the AKT and AR signal pathways. AU - Yang,Yang, AU - Ikezoe,Takayuki, AU - Takeuchi,Tamotsu, AU - Adachi,Yoshihiro, AU - Ohtsuki,Yuji, AU - Koeffler,H Phillip, AU - Taguchi,Hirokuni, PY - 2006/5/11/pubmed PY - 2007/3/9/medline PY - 2006/5/11/entrez SP - 1581 EP - 90 JF - Oncology reports JO - Oncol. Rep. VL - 15 IS - 6 N2 - Zanthoxyli Fructus belongs to the family of oranges and is used as a seasoning in Asian countries including Japan. This study found that a water extract of Zanthoxyli Fructus possessed anti-tumor activity against a wide variety of cancer cells including those from prostate (LNCaP, DU145, PC-3), breast (MCF-7, T47D, MDA-MB231), lung (NCI-H460, -H520), as well as leukemia (HL-60, NB4, Jurkat) in vitro, as measured by the trypan blue exclusion test. Importantly, Zanthoxyli Fructus slowed the proliferation of LNCaP, DU145, and MDA-MB231 cells present as xenografts in BALB/c nude mice without adverse effects. Further studies explored the molecular mechanism by which Zanthoxyli Fructus inhibited the proliferation of androgen-dependent human prostate cancer LNCaP cells because Zanthoxyli Fructus possessed the strongest anti-tumor activity against these cells. Zanthoxyli Fructus blocked androgen receptor (AR) signaling in conjunction with down-regulation of nuclear levels of AR and induced apoptosis of these cells, as measured by the reporter assay, Western blot analysis, and TUNEL assay, respectively. As expected, Zanthoxyli Fructus also decreased the level of the AR-target molecule, prostate-specific antigen in these cells. Furthermore, Zanthoxyli Fructus inhibited AKT kinase and down-regulated levels of cyclin D1 protein, as measured by the AKT kinase assay with GSK-3alpha/beta as a substrate and Western blot analysis, respectively. Taken together, Zanthoxyli Fructus might be useful as an adjunctive therapeutic agent for the treatment of individuals with a variety of cancer types. SN - 1021-335X UR - https://www.unboundmedicine.com/medline/citation/16685399/Zanthoxyli_Fructus_induces_growth_arrest_and_apoptosis_of_LNCaP_human_prostate_cancer_cells_in_vitro_and_in_vivo_in_association_with_blockade_of_the_AKT_and_AR_signal_pathways_ L2 - http://www.spandidos-publications.com/or/15/6/1581 DB - PRIME DP - Unbound Medicine ER -