Norcantharidin is a small-molecule synthetic compound with anti-angiogenesis effect

Chen, Yu-Jen; Tsai, Yin-Meng; Kuo, Cheng‐Deng; Ku, Kuo-Lung; Shie, Huei-Sian; Liao, Hui-Fen

doi:10.1016/j.lfs.2009.09.003

Cited by 45 publications

(29 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NCTD is a demethylated CTD analog [25][26][27]. In addition to inhibition of the proliferation of a range of cancer-specific cells, NCTD potently inhibits angiogenesis and breast cancer cell-line metastases, without significant renal or liver toxicity [28][29][30][31][32][33][34].…”

Section: Introductionmentioning

confidence: 99%

Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling

Cimmino¹,

Scoppettuolo²,

Carotenuto³

et al. 2011

J Neurooncol

View full text Add to dashboard Cite

Medulloblastoma is one of the leading causes of morbidity and mortality in pediatric cancer. Wnt-active tumors, an independent molecular subgroup in medulloblastoma, are characterized by a distinct pattern of genomic aberrations. We assessed the anticancer activity of cantharidin and norcantharidin against medulloblastoma, as cell lines in vitro and in athymic nude mice in vivo. Cantharidin and norcantharidin treatment impaired the growth of DAOY and UW228 medulloblastoma cells and promoted the loss of β-catenin activation and the β-catenin nuclearization linked to N-cadherin impairment in vitro. Intra-peritoneal administration of norcantharidin inhibited the growth of intra-cerebellum tumors in orthotopic xenograft nude mice. Analysis of the xenograft tissues revealed enhanced neuronal differentiation and reduced β-catenin expression. Our findings suggest that norcantharidin has potential therapeutic applications in the treatment of medulloblastoma as a result of its ability to cross the blood-brain barrier and its impairment of Wnt-β-catenin signaling.

show abstract

Section: Introductionmentioning

confidence: 99%

Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling

Cimmino¹,

Scoppettuolo²,

Carotenuto³

et al. 2011

J Neurooncol

View full text Add to dashboard Cite

show abstract

“…or M. cichoril L.) has been used in traditional Chinese medicine for the treatment of malignant tumors by its main content cantharidin for more than 1000 years. Norcantharidin (NCTD, (1S,2R,3S,4R)-7-oxabicyclo- [2,2,1] heptane-2,3-dicarboxylic anhydride), the demethylated analogue of cantharidin, inhibits the proliferation of a variety of human tumor cell lines [1][2][3][4][5][6][7][8][9][10][11], and appears to cause the least nephrotoxic and inflammatory side effects. Moreover, NCTD is not a substrate for the P-glycoprotein pump, a known mechanism for developing cancer resistance [6,7].…”

Section: Introductionmentioning

confidence: 99%

Separation and identification of norcantharidin metabolites in vivo by GC–MS method

Wei¹,

Teng²,

Wang³

et al. 2011

Journal of Chromatography B

View full text Add to dashboard Cite

“…It has been shown that NCTD inhibits angiogenesis [29,30], induces DNA damage and ROS-mediated mitochondrial dysfunction [31,32], suppresses proliferation [33][34][35], invasion and migration [36], increases apoptosis [37][38][39], possesses anticancer activity via TR3, PKC, PI3-K/MMPs/ Ln-5c2, MAPK [40], VEGFR2/MEK/ERK [41] signal pathways and so on.…”

Section: Discussionmentioning

confidence: 99%

Norcantharidin inhibits Wnt signal pathway via promoter demethylation of WIF-1 in human non-small cell lung cancer

Xie

Zhang

et al. 2015

Med Oncol

View full text Add to dashboard Cite

Wingless-type (Wnt) family of secreted glycoproteins is a group of signal molecules implicated in oncogenesis. Abnormal activation of Wnt signal pathway is associated with a variety of human cancers, including non-small cell lung cancer (NSCLC). Wnt antagonists, such as the secreted frizzled-related protein (SFRP) family, Wnt inhibitory factor-1 (WIF-1) and cerberus, inhibit Wnt signal pathway by directly binding to Wnt molecules. Norcantharidin (NCTD) is known to possess anticancer activity but less nephrotoxicity than cantharidin. In this study, we found that NCTD inhibited cell proliferation, induced apoptosis, arrested cell cycle and suppressed cell invasion/migration in vitro. Additionally, Wnt signal pathway transcription was also suppressed. NCTD treatment blocked cytoplasmic translocation of beta-catenin into the nucleus. Alterations of apoptosis-related proteins, such as Bax, cleaved caspase-3 (pro-apoptotic) and Bcl-2 (anti-apoptotic), had been detected. Furthermore, the expression levels of WIF-1 and SFRP1 were significantly increased in NCTD-treated groups compared with negative control (NC) groups. Abnormal methylation was observed in NC groups, while NCTD treatment promoted WIF-1 demethylation. The present study revealed that NCTD activated WIF-1 via promoter demethylation, inhibiting the canonical Wnt signal pathway in NSCLC, which may present a new therapeutic target in vivo.

show abstract

Norcantharidin is a small-molecule synthetic compound with anti-angiogenesis effect

Cited by 45 publications

References 25 publications

Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling

Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling

Separation and identification of norcantharidin metabolites in vivo by GC–MS method

Norcantharidin inhibits Wnt signal pathway via promoter demethylation of WIF-1 in human non-small cell lung cancer

Contact Info

Product

Resources

About