SUCI02 inhibits the erbB‐2 tyrosine kinase receptor signaling pathway and arrests the cell cycle in G<sub>1</sub> phase in breast cancer cells

Zhu, Xiao Feng; Wang, Jingsong; Cai, Li; Zeng, Yi Xin; Yang, Dajun

doi:10.1111/j.1349-7006.2006.00143.x

Cited by 17 publications

(15 citation statements)

References 19 publications

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“…Indeed, the blockage of EGFR-signaling cascades seemingly increased the levels of p27 and p21 proteins, which in turn inhibited the CDK family proteins and repressed cellular proliferation by impairment of G 1 phase progression and entry into S phase. 37,38 It has been shown that blockage of EGFR cascades resulted in the inhibition of proliferation of prostate cancer cell lines via G 1 arrest. 39 Both PI3K and Akt, a serine/threonine protein kinase and downstream effecter of PI3K, are part of a signaling pathway that can be initiated by EGFR activation.…”

Section: Discussionmentioning

confidence: 99%

NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and mdulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts

Selvendiran

Bratasz²,

Tong³

et al. 2008

Cell Cycle

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We have previously reported the inhibitory effect of NCX-4016, a nitro derivative of aspirin, on the proliferation of cisplatin-resistant human ovarian cancer cells, in vitro (Bratasz et al., Proc Natl Acad Sci USA 2006; 103:3914-9). In this report we present the results of our study on the mechanistic aspects of drug action including the molecular and signaling pathways involved in an in vitro cell line, as well as in a murine tumor xenograft. We report, for the first time, that NCX-4016 significantly inhibited the growth of cisplatin-resistant human ovarian cancer xenografts in mice. We observed that the inhibitory effect of NCX-4016 on cell proliferation was associated with G 1 phase cell cycle arrest with increased activity of p53, p21 and p27 proteins. NCX-4016 modulated the Bcl-2 family of proteins, and induced apoptosis by activating Bax and cytochrome c release in a time-dependent manner. In addition, NCX-4016 selectively down-regulated the phosphorylated forms of EGFR (Tyr845, Tyr992), pAkt (Ser473, Thr305), and STAT3 (Tyr705, Ser727), in vitro and in vivo. Taken together, the results clearly suggested that NCX-4016 causes significant induction of cell cycle arrest and apoptosis in cisplatin-resistant human ovarian cancer cells via down-regulation of EGFR/PI3K/STAT3 signaling and modulation of Bcl-2 family proteins. Thus, NCX-4016 appears to be a potential therapeutic agent for treating recurrent human ovarian carcinoma.

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Section: Discussionmentioning

confidence: 99%

NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and mdulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts

Selvendiran

Bratasz²,

Tong³

et al. 2008

Cell Cycle

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“…Anti-HER2/neu targeting therapies such as trastuzumab and lapatinib already improve clinical outcomes (Ono et al, 2004;Guan et al, 2005;Henson et al, 2006;Esteva, 2005, 2006;Safran et al, 2004;Locati et al, 2005;Cho et al, 2005;Liang et al, 2003;Suarez et al, 2003;Scott et al, 2002;Yardley et al, 2010). The success of trastuzumab clearly demonstrates the therapeutic value of a molecular therapy targeted against HER2/neu and drives the design and development of other HER2/neu-targeted therapies (Zhu et al, 2006;Toulany et al, 2006;Wulfing et al, 2006;Baselga, 2010).…”

Section: Introductionmentioning

confidence: 94%

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

et al. 2012

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“…The synthesis of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (ON-III) was described previously. 24 Its ON-III inhibited erbB-2 tyrosine kinase receptor signal pathway for 1 h at room temperature. Being washed with TBST, the bound antibody complex was detected using an ECL chemiluminescence reagent and XAR film (Kodak) as described by the manufacturer (Amersham).…”

Section: Methodsmentioning

confidence: 99%

“…Cells treated with ON-III were washed with PBS, and lysed in 120 μl of lysis buffer. 24 Lysates were centrifuged at 12,000 rpm for 15 min. The supernatant was collected.…”

Section: Methodsmentioning

confidence: 99%

ON-III inhibits erbB-2 tyrosine kinase receptor signal pathway and triggers apoptosis through induction of Bim in breast cancer cells

Li¹,

Tang

et al. 2009

Cancer Biology & Therapy

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ErbB-2 gene encodes tyrosine kinase receptor p185(neu). Overexpression of erbB-2 plays a key role in tumorigenesis or progression such as breast cancer and ovarian cancer. Our previous study showed that ON-III (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone) extracted from Traditional Chinese Medicine Cleistocaly xoperculatus dry flower could inhibit KDR tyrosine kinase phosphorylation and tumor growth in vivo. In this study, we reported that ON-III repressed tyrosine phosphorylation of erbB-2 without reduced erbB-2 receptor expression in MDA-MB-453 cells. Activation of mitogen-activated protein kinase (MAPK) and AKT, downstream molecules of erbB-2-mediated signal transduction pathway, was inhibited following exposure to ON-III. ON-III induced apoptosis in breast cancer cells as determined by caspase-3 and PARP cleavage. Also, ON-III upregulated the expression of proapoptotic BH3-only Bcl-2 family member Bim. Bim siRNA could inhibit ON-III-mediated apoptosis in MDA-MB-453 cells. It concludes that ON-III inhibits erbB-2 tyrosine kinase phosphorylation, shuts down its downstream pathway and triggered apoptosis via induction of Bim. These results suggest that ON-III is a potential novel anti-cancer agent for erbB-2-overexpressing cancer.

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SUCI02 inhibits the erbB‐2 tyrosine kinase receptor signaling pathway and arrests the cell cycle in G₁ phase in breast cancer cells

Cited by 17 publications

References 19 publications

NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and mdulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts

NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and mdulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts

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

ON-III inhibits erbB-2 tyrosine kinase receptor signal pathway and triggers apoptosis through induction of Bim in breast cancer cells

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SUCI02 inhibits the erbB‐2 tyrosine kinase receptor signaling pathway and arrests the cell cycle in G1 phase in breast cancer cells

Cited by 17 publications

References 19 publications

NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and mdulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts

NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and mdulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts

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

ON-III inhibits erbB-2 tyrosine kinase receptor signal pathway and triggers apoptosis through induction of Bim in breast cancer cells

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SUCI02 inhibits the erbB‐2 tyrosine kinase receptor signaling pathway and arrests the cell cycle in G₁ phase in breast cancer cells