3,4-Methylenedioxy-β-nitrostyrene inhibits adhesion and migration of human triple-negative breast cancer cells by suppressing β1 integrin function and surface protein disulfide isomerase

Chen, I-Hua; Chang, Fang‐Rong; Wu, Yang‐Chang; Kung, Po-Hsiung; Wu, Chueh-Hung

doi:10.1016/j.biochi.2015.01.006

Cited by 36 publications

(32 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, two β-nitrostyrene derivative compounds NTS1 and NTS2 induced apoptosis through cytochrome c release from mitochondria to cytosol and caspase activation in Ehrlich ascitic tumor cells [16]. Recently, the inhibitory effect of 3,4-methylenedioxy-β-nitrostyrene on breast cancer cell adhesion and migration was demonstrated by suppressing β1 integrin and surface protein disulfide isomerase [17]. …”

Section: Introductionmentioning

confidence: 99%

The Synthetic β-Nitrostyrene Derivative CYT-Rx20 Inhibits Esophageal Tumor Growth and Metastasis via PI3K/AKT and STAT3 Pathways

Chiu

Lee

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

The β-nitrostyrene family have been implicated for anti-cancer property. However, the pharmacological role of β-nitrostyrene in esophageal cancer remain unclear. Here, a β-nitrostyrene derivative, CYT-Rx20, was synthesized and assessed for its anti-cancer activities and underlying mechanism in esophageal cancer. CYT-Rx20 induced cytotoxicity in esophageal cancer cells by promoting apoptosis through activation of caspase cascade and poly(ADP-ribose) polymerase (PARP) cleavage. Besides, CYT-Rx20 inhibited esophageal cancer cell migration and invasion by regulating the expression of epithelial to mesenchymal transition (EMT) markers. CYT-Rx20 decreased cell viability and migration through suppression of the PI3K/AKT and STAT3 pathways. Of note, the cytotoxicity and anti-migratory effect of CYT-Rx20 were enhanced by co-treatment with SC79 (AKT activator) or colivelin (STAT3 activator), suggesting the dependency of esophageal cancer cells on AKT and STAT3 for survival and migration, an oncogene addiction phenomenon. In xenograft tumor-bearing mice, CYT-Rx20 significantly reduced tumor growth of the implanted esophageal cancer cells accompanied by decreased Ki-67, phospho-AKT, and phospho-STAT3 expression. In orthotopic esophageal cancer mouse model, decreased tumor growth and lung metastasis with reduced Ki-67 and phospho-STAT3 expression were observed in mice treated with CYT-Rx20. Together, our results suggest that CYT-Rx20 is a potential β-nitrostyrene-based anticancer compound against the tumor growth and metastasis of esophageal cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

The Synthetic β-Nitrostyrene Derivative CYT-Rx20 Inhibits Esophageal Tumor Growth and Metastasis via PI3K/AKT and STAT3 Pathways

Chiu

Lee

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…A synthesized compound of PKCzI257.3 which inhibits EGF-induced breast cancer cell migration by suppressing PKCz [16]. 3,4-methyenedioxy-b-nitrostyrene inhibits in vitro metastatic properties of triple negative breast cancer cells through suppression of b1 integrin activation and focal adhesion signaling [17]. In addition, Ginsenoside Rp1 down-regulates integrin b1 activation at concentrations between 10 to 40 mM and suppresses the in vitro tube formation of HUVEC [18].…”

Section: Anti-invasive Activitymentioning

confidence: 99%

Synthesis and anti-metastatic effects of novel chiral ionone alkaloid derivatives

Fang

Shou

Liu

et al. 2015

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

“…The β-nitrostyrene family and its derivatives have been found to exert various biological effects including antimicrobial, antiplatelet, anti-inflammatory, and anticancer activities [7–13]. For example, 3, 4-methylenedioxy-β-nitrostyrene exhibited inhibitory effects on ATPase and decreased inflammasome activation [10].…”

Section: Introductionmentioning

confidence: 99%

3’-hydroxy-4’-methoxy-β-methyl-β-nitrostyrene inhibits tumorigenesis in colorectal cancer cells through ROS-mediated DNA damage and mitochondrial dysfunction

et al. 2017

View full text Add to dashboard Cite

The β-nitrostyrene family has been shown to suppress cell proliferation and induce apoptosis in types of various cancers. However, the mechanisms underlying the anticancer effects of β-nitrostyrenes in colorectal cancer remain poorly understood. In this study, we synthesized a β-nitrostyrene derivative, CYT-Rx20 (3’-hydroxy-4’-methoxy-β-methyl-β-nitrostyrene), and investigated its anticancer activities in human colorectal cancer cells both in vitro and in vivo. Our findings showed that treatment with CYT-Rx20 reduced cell viability and induced DNA damage in colorectal cancer cells. In addition, CYT-Rx20 induced cell cycle arrest of colorectal cancer cells at the G2/M phase and upregulated the protein expression of phospho-ERK, cyclin B1, phospho-cdc2 (Tyr15), aurora A, and aurora B, while it downregulated the expression of cdc25A and cdc25C. Furthermore, we found that CYT-Rx20 caused accumulation of intracellular reactive oxygen species (ROS) and reduction of mitochondrial membrane potential. The effects of CYT-Rx20 on cell viability, DNA damage, and mitochondrial membrane potential were reversed by pretreatment with the thiol antioxidant N-acetyl-L-cysteine (NAC), suggesting that ROS-mediated DNA damage and mitochondrial dysregulation play a critical role in these events. Finally, the nude mice xenograft study showed that CYT-Rx20 significantly reduced tumor growth of implanted colorectal cancer cells accompanied by elevated protein expression of aurora A, aurora B, γH2AX, phosphor-ERK, and MDA in the tumor tissues. Taken together, these results suggest that CYT-Rx20 may potentially be developed as a novel β-nitrostyrene-based anticancer agent for colorectal cancer.

show abstract

3,4-Methylenedioxy-β-nitrostyrene inhibits adhesion and migration of human triple-negative breast cancer cells by suppressing β1 integrin function and surface protein disulfide isomerase

Cited by 36 publications

References 57 publications

The Synthetic β-Nitrostyrene Derivative CYT-Rx20 Inhibits Esophageal Tumor Growth and Metastasis via PI3K/AKT and STAT3 Pathways

The Synthetic β-Nitrostyrene Derivative CYT-Rx20 Inhibits Esophageal Tumor Growth and Metastasis via PI3K/AKT and STAT3 Pathways

Synthesis and anti-metastatic effects of novel chiral ionone alkaloid derivatives

3’-hydroxy-4’-methoxy-β-methyl-β-nitrostyrene inhibits tumorigenesis in colorectal cancer cells through ROS-mediated DNA damage and mitochondrial dysfunction

Contact Info

Product

Resources

About