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

Zhou, Ning; Tang, Jun; Chen, Wen Dan; Feng, Gong Kan; Xie, Bingteng; Liu, Zong Chao; Yang, Dajun; Zhu, Xiao Feng

doi:10.1016/j.lfs.2012.03.035

Cited by 22 publications

(16 citation statements)

References 36 publications

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“…Phosphorylation of HER2 receptor tyrosine kinase activates the MAPK and PI3K/AKT signaling pathways, which in turn promotes the cell proliferation and metastasis [30]–[33]. MAPK and PI3K/AKT, which are major pathways involved in the malignant progression of various tumors, mediate the proliferation, migration and invasion of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

BMP9 Inhibits Proliferation and Metastasis of HER2-Positive SK-BR-3 Breast Cancer Cells through ERK1/2 and PI3K/AKT Pathways

et al. 2014

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Bone morphogenetic protein 9 (BMP9), a member of TGF-β superfamily, is reported to inhibit the growth and migration of prostate cancer, osteosarcoma and triple-negative MDA-MB-231 breast cancer cells. However, little is known about the effect of on the biological behaviors of HER2-positive SK-BR-3 breast cancer cells and the underlying mechanisms. This study aimed to investigate the effects of BMP9 on the proliferation and metastasis of SK-BR-3 cells with BMP9 over-expression or BMP9 down-regulated expression. Results indicated that exogenously expressed BMP9 inhibited the proliferation and metastasis of SK-BR-3 cells while decreased endogenous BMP9 expression in SK-BR-3 cells promoted the proliferation and migration of breast cancer cells in vitro and in vivo. In SK-BR-3 cells with BMP9 over-expression, the phosphorylation of HER2, ERK1/2 and AKT was markedly suppressed and the HER2 expression decreased at both mRNA and protein levels, while opposite results were observed in SK-BR-3 cells with BMP9 knock down. When the phosphorylation of ERK1/2 and PI3K/AKT was inhibited by PD98059 and LY294002, respectively, the decreased proliferation and invasion induced by BMP9 knock down were eliminated. These findings suggest that BMP9 can inhibit the proliferation and metastasis of SK-BR-3 cells via inactivating ERK1/2 and PI3K/AKT signaling pathways. Thus, BMP9 may serve as a useful agent in the treatment of HER-2 positive breast cancer.

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Section: Discussionmentioning

confidence: 99%

BMP9 Inhibits Proliferation and Metastasis of HER2-Positive SK-BR-3 Breast Cancer Cells through ERK1/2 and PI3K/AKT Pathways

et al. 2014

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“…As a medicinal plant, it has been reported to possess important biological properties such as anticancer [2][3][4][5][6][7] , antiviral 8,9 , antioxidant 10,11 , and antiinflammatory activities 12,13 . In Thailand, many of H. cordata fermentation products are commercially available, however, the anticancer activity of these commercialized products remains to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Phenolic acid composition and anticancer activity against human cancer cell lines of the commercially available fermentation products of Houttuynia cordata

Senawong¹,

Khaopha²,

Misuna³

et al. 2014

ScienceAsia

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A number of Houttuynia cordata fermentation products are commercially available in Thailand. However, their anticancer activity remains to be investigated. In this study, the phenolic acid composition and anticancer activity of two commercialized H. cordata fermentation products were investigated. Reversed phase HPLC was used to identify and quantify phenolic acids. MTT and Annexin V staining assays were used to investigate antiproliferative and apoptosis induction activities, respectively. Seven phenolic acids including protocatechuic, p-hydroxybenzoic, vanillic, syringic, p-coumaric, ferulic, and sinapinic acids were detected in the water-soluble constituents of both fermentation products 1 and 2. Water-soluble constituents of fermentation product 2 containing a greater phenolic acid content were more effective than product 1 in inhibiting the growth of HeLa, HCT116, and HT29 cells in a dose-and time-dependent manner. The non-cancer cell line Vero cells appeared to be resistant to both fermentation products. The growth inhibitory effects of both fermentation products in HeLa, HCT116, and HT29 cells included induction of apoptosis. These results suggest that commercially available fermentation products of H. cordata contain several anticancer phenolic acids that may be beneficial in the treatment of human cancer.

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“…Thus emphasizing the requirement for further research into the molecular mechanisms of HCC development, and identification of non-cytotoxic and effective antineoplastic compounds for chemoprevention and treatment. Recently, more traditional herbal medicines are being considered for use as anticancer treatments (20)(21)(22). However, few anticancer agents with low toxicity have been identified to be safe and effective for the treatment of HCC.…”

Section: Discussionmentioning

confidence: 99%

Anticancer agent icaritin induces apoptosis through caspase-dependent pathways in human hepatocellular carcinoma cells

Sun

Peng

et al. 2014

Molecular Medicine Reports

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Abstract.Icaritin is an active ingredient derived from the plant Herba epimedium, which exhibits various pharmacological and biological activities. However, the function, and the underlying mechanisms of icaritin on the growth of SMMC-7721 human hepatoma cells have yet to be elucidated. The present study aimed to investigate the function and underlying mechanisms of icaritin in the growth of SMMC-7721 cells. The cells were treated with varying concentrations of icaritin for 12, 24 and 48 h, respectively, prior to cytotoxic analysis. Apoptosis of SMMC-7721 cells following treatment with icaritin was measured using flow cytometry. The gene expression of mitochondria-and Fas-mediated caspase-dependent pathways was detected by reverse transcription-quantitative polymerase chain reaction and western blotting. Statistical analysis was performed by Student's t-test and one-way analysis or variance. The present study demonstrated that treatment with icaritin significantly inhibited growth, and induced apoptosis of SMMC-7721 cells, in a time-and dose-dependent manner. In addition, icaritin triggered the mitochondrial/caspase apoptotic pathway, by decreasing the Bcl-2/Bax protein ratio and increasing activation of caspase-3. Icaritin also activated the Fas-mediated apoptosis pathway, as was evident by the increased expression levels of Fas and activation of caspase-8. These data suggest that icaritin may be a potent growth inhibitor and induce apoptosis of SMMC-7721 cells through the mitochondria-and Fas-mediated caspase-dependent pathways. The present study may provide experimental evidence for preclinical and clinical evaluations of icaritin for HCC therapy.

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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

Cited by 22 publications

References 36 publications

BMP9 Inhibits Proliferation and Metastasis of HER2-Positive SK-BR-3 Breast Cancer Cells through ERK1/2 and PI3K/AKT Pathways

BMP9 Inhibits Proliferation and Metastasis of HER2-Positive SK-BR-3 Breast Cancer Cells through ERK1/2 and PI3K/AKT Pathways

Phenolic acid composition and anticancer activity against human cancer cell lines of the commercially available fermentation products of Houttuynia cordata

Anticancer agent icaritin induces apoptosis through caspase-dependent pathways in human hepatocellular carcinoma cells

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