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Houttuyninum, an active constituent of Chinese herbal medicine, inhibits phosphorylation of HER2/neu receptor tyrosine kinase and the tumor growth of HER2/neu-overexpressing cancer cells.
Life Sci. 2012 May 22; 90(19-20):770-5.LS

Abstract

AIMS

The overexpression of HER2/neu receptor plays a key role in tumorigenesis and tumor progression. Small molecules targeting HER2/neu have therapeutic value in cancers that overexpress HER2. In this present study, the effect of houttuyninum, a component in the Chinese herbal medicine Houttuynia cordata Thunb, on HER2/neu tyrosine phosphorylation and its in vivo antitumour activity was investigated.

MAIN METHODS

The phosphorylation and expression of proteins were determined by Western blot analysis. The MTT assay was employed to examine the inhibition of cell proliferation in vitro. Xenografts were established in nude mice for evaluating the antitumour activity of houttuyninum in vivo.

KEY FINDINGS

Houttuyninum inhibited phosphorylation of HER2 in a dose-dependent manner with an IC50 of 5.52 μg/ml without reducing HER2/neu protein expression in MDA-MB-453 cells. Houttuyninum also inhibited the activation of ERK1/2 and AKT, downstream molecules in the HER2/neu-mediated signal transduction pathway. In contrast, tyrosine phosphorylation of EGFR was unaffected when the concentration of houttuyninum was increased to 40 μg/ml in both A431 cells and MDA-MB-468 cells. Additionally, houttuyninum preferentially inhibited the growth of MDA-MB-453 cells that overexpressed HER2/neu; the MDA-MB-468 cells that overexpress EGFR remained unaffected. Administration of houttuyninum in vivo resulted in a significant reduction of phosphorylated HER2 levels and in tumor volumes of the BT474 and N87 xenografts, which both overexpress HER2/neu.

SIGNIFICANCE

Our findings showed that houttuyninum can inhibit the HER2/neu signalling pathway and the tumor growth of cancer cells that overexpress HER2/neu. This drug may provide therapeutic value in the treatment of cancers that involve overexpression of HER2/neu.

Authors+Show Affiliations

State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, PR China.No affiliation info availableNo 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, Non-U.S. Gov't

Language

eng

PubMed ID

22525372

Citation

Zhou, Ning-Ning, et al. "Houttuyninum, an Active Constituent of Chinese Herbal Medicine, Inhibits Phosphorylation of HER2/neu Receptor Tyrosine Kinase and the Tumor Growth of HER2/neu-overexpressing Cancer Cells." Life Sciences, vol. 90, no. 19-20, 2012, pp. 770-5.
Zhou NN, Tang J, Chen WD, et al. Houttuyninum, an active constituent of Chinese herbal medicine, inhibits phosphorylation of HER2/neu receptor tyrosine kinase and the tumor growth of HER2/neu-overexpressing cancer cells. Life Sci. 2012;90(19-20):770-5.
Zhou, N. N., Tang, J., Chen, W. D., Feng, G. K., Xie, B. F., Liu, Z. C., Yang, D., & Zhu, X. F. (2012). Houttuyninum, an active constituent of Chinese herbal medicine, inhibits phosphorylation of HER2/neu receptor tyrosine kinase and the tumor growth of HER2/neu-overexpressing cancer cells. Life Sciences, 90(19-20), 770-5. https://doi.org/10.1016/j.lfs.2012.03.035
Zhou NN, et al. Houttuyninum, an Active Constituent of Chinese Herbal Medicine, Inhibits Phosphorylation of HER2/neu Receptor Tyrosine Kinase and the Tumor Growth of HER2/neu-overexpressing Cancer Cells. Life Sci. 2012 May 22;90(19-20):770-5. PubMed PMID: 22525372.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Houttuyninum, an active constituent of Chinese herbal medicine, inhibits phosphorylation of HER2/neu receptor tyrosine kinase and the tumor growth of HER2/neu-overexpressing cancer cells. AU - Zhou,Ning-Ning, AU - Tang,Jun, AU - Chen,Wen-Dan, AU - Feng,Gong-Kan, AU - Xie,Bin-Fen, AU - Liu,Zong-Chao, AU - Yang,Dajun, AU - Zhu,Xiao-Feng, Y1 - 2012/04/13/ PY - 2011/10/17/received PY - 2012/03/15/revised PY - 2012/03/28/accepted PY - 2012/4/25/entrez PY - 2012/4/25/pubmed PY - 2012/6/27/medline SP - 770 EP - 5 JF - Life sciences JO - Life Sci VL - 90 IS - 19-20 N2 - AIMS: The overexpression of HER2/neu receptor plays a key role in tumorigenesis and tumor progression. Small molecules targeting HER2/neu have therapeutic value in cancers that overexpress HER2. In this present study, the effect of houttuyninum, a component in the Chinese herbal medicine Houttuynia cordata Thunb, on HER2/neu tyrosine phosphorylation and its in vivo antitumour activity was investigated. MAIN METHODS: The phosphorylation and expression of proteins were determined by Western blot analysis. The MTT assay was employed to examine the inhibition of cell proliferation in vitro. Xenografts were established in nude mice for evaluating the antitumour activity of houttuyninum in vivo. KEY FINDINGS: Houttuyninum inhibited phosphorylation of HER2 in a dose-dependent manner with an IC50 of 5.52 μg/ml without reducing HER2/neu protein expression in MDA-MB-453 cells. Houttuyninum also inhibited the activation of ERK1/2 and AKT, downstream molecules in the HER2/neu-mediated signal transduction pathway. In contrast, tyrosine phosphorylation of EGFR was unaffected when the concentration of houttuyninum was increased to 40 μg/ml in both A431 cells and MDA-MB-468 cells. Additionally, houttuyninum preferentially inhibited the growth of MDA-MB-453 cells that overexpressed HER2/neu; the MDA-MB-468 cells that overexpress EGFR remained unaffected. Administration of houttuyninum in vivo resulted in a significant reduction of phosphorylated HER2 levels and in tumor volumes of the BT474 and N87 xenografts, which both overexpress HER2/neu. SIGNIFICANCE: Our findings showed that houttuyninum can inhibit the HER2/neu signalling pathway and the tumor growth of cancer cells that overexpress HER2/neu. This drug may provide therapeutic value in the treatment of cancers that involve overexpression of HER2/neu. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/22525372/Houttuyninum_an_active_constituent_of_Chinese_herbal_medicine_inhibits_phosphorylation_of_HER2/neu_receptor_tyrosine_kinase_and_the_tumor_growth_of_HER2/neu_overexpressing_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(12)00173-7 DB - PRIME DP - Unbound Medicine ER -