Tags

Type your tag names separated by a space and hit enter

Magnolol down-regulates HER2 gene expression, leading to inhibition of HER2-mediated metastatic potential in ovarian cancer cells.
Cancer Lett. 2011 Dec 01; 311(1):11-9.CL

Abstract

Overexpression of the HER2 oncogene contributes to tumor cell invasion, metastasis and angiogenesis and correlates with poor prognosis. Magnolol has been reported to exhibit anti-tumor activities. However, the molecular mechanism of action of magnolol has not been investigated in HER2-positive cancer cells. Therefore, we examined the anti-cancer effects of magnolol on HER2-overexpressing ovarian cancer cells. Magnolol treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level, potentially in part through suppression of NF-κB activation. Treatment of HER2-overexpressing ovarian cancer cells with magnolol down-regulated the HER2 downstream PI3K/Akt signaling pathway, and suppressed the expression of downstream target genes, vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2) and cyclin D1. Consistently, magnolol-mediated inhibition of MMP2 activity could be prevented by co-treatment with epidermal growth factor. Migration assays revealed that magnolol treatment markedly reduced the motility of HER2-overexpressing ovarian cancer cells. Furthermore, magnolol-induced apoptosis in HER2-overexpressing ovarian cancer cells was characterized by the up-regulation of cleaved poly(ADP-ribose) polymerase (PARP) and activated caspase 3. These findings suggest that magnolol may act against HER2 and its downstream PI3K/Akt/mTOR-signaling network, thus resulting in suppression of HER2-mediated transformation and metastatic potential in HER2-overexpressing ovarian cancers. These results provide a novel mechanism to explain the anti-cancer effect of magnolol.

Authors+Show Affiliations

Department of Chemistry, Tamkang University, New Taipei, Taiwan, ROC. tcbc@mail.tku.edu.twNo 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

21757288

Citation

Chuang, Tzu-Chao, et al. "Magnolol Down-regulates HER2 Gene Expression, Leading to Inhibition of HER2-mediated Metastatic Potential in Ovarian Cancer Cells." Cancer Letters, vol. 311, no. 1, 2011, pp. 11-9.
Chuang TC, Hsu SC, Cheng YT, et al. Magnolol down-regulates HER2 gene expression, leading to inhibition of HER2-mediated metastatic potential in ovarian cancer cells. Cancer Lett. 2011;311(1):11-9.
Chuang, T. C., Hsu, S. C., Cheng, Y. T., Shao, W. S., Wu, K., Fang, G. S., Ou, C. C., & Wang, V. (2011). Magnolol down-regulates HER2 gene expression, leading to inhibition of HER2-mediated metastatic potential in ovarian cancer cells. Cancer Letters, 311(1), 11-9. https://doi.org/10.1016/j.canlet.2011.06.007
Chuang TC, et al. Magnolol Down-regulates HER2 Gene Expression, Leading to Inhibition of HER2-mediated Metastatic Potential in Ovarian Cancer Cells. Cancer Lett. 2011 Dec 1;311(1):11-9. PubMed PMID: 21757288.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Magnolol down-regulates HER2 gene expression, leading to inhibition of HER2-mediated metastatic potential in ovarian cancer cells. AU - Chuang,Tzu-Chao, AU - Hsu,Shih-Chung, AU - Cheng,Yi-Ting, AU - Shao,Wei-Syun, AU - Wu,Kuohui, AU - Fang,Guan-Shiun, AU - Ou,Chien-Chih, AU - Wang,Vinchi, Y1 - 2011/06/25/ PY - 2011/03/17/received PY - 2011/06/09/revised PY - 2011/06/12/accepted PY - 2011/7/16/entrez PY - 2011/7/16/pubmed PY - 2011/12/13/medline SP - 11 EP - 9 JF - Cancer letters JO - Cancer Lett. VL - 311 IS - 1 N2 - Overexpression of the HER2 oncogene contributes to tumor cell invasion, metastasis and angiogenesis and correlates with poor prognosis. Magnolol has been reported to exhibit anti-tumor activities. However, the molecular mechanism of action of magnolol has not been investigated in HER2-positive cancer cells. Therefore, we examined the anti-cancer effects of magnolol on HER2-overexpressing ovarian cancer cells. Magnolol treatment caused a dose-dependent inhibition of HER2 gene expression at the transcriptional level, potentially in part through suppression of NF-κB activation. Treatment of HER2-overexpressing ovarian cancer cells with magnolol down-regulated the HER2 downstream PI3K/Akt signaling pathway, and suppressed the expression of downstream target genes, vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP2) and cyclin D1. Consistently, magnolol-mediated inhibition of MMP2 activity could be prevented by co-treatment with epidermal growth factor. Migration assays revealed that magnolol treatment markedly reduced the motility of HER2-overexpressing ovarian cancer cells. Furthermore, magnolol-induced apoptosis in HER2-overexpressing ovarian cancer cells was characterized by the up-regulation of cleaved poly(ADP-ribose) polymerase (PARP) and activated caspase 3. These findings suggest that magnolol may act against HER2 and its downstream PI3K/Akt/mTOR-signaling network, thus resulting in suppression of HER2-mediated transformation and metastatic potential in HER2-overexpressing ovarian cancers. These results provide a novel mechanism to explain the anti-cancer effect of magnolol. SN - 1872-7980 UR - https://www.unboundmedicine.com/medline/citation/21757288/Magnolol_down_regulates_HER2_gene_expression_leading_to_inhibition_of_HER2_mediated_metastatic_potential_in_ovarian_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(11)00343-0 DB - PRIME DP - Unbound Medicine ER -