|Description:||1. Norcantharidin(NCTD) has been used to treat human cancers in China since 1984. |
2. Norcantharidin, a protein phosphatase type-2A inhibitor, which has less nephrotoxic and phlogogenic side-effects, it can inhibit both DNA synthesis and granulocyte-macrophage colony-forming cells (GM-CFC)growth and impaire the neogenesis of chromatin material and nuclear membrane during the M/G1 phase transition in K-562 cells.
3. Norcantharidin inhibits the canonical Wnt signal pathway in NSCLC, by activating WIF-1 via promoter demethylation.
4. Norcantharidin could be an effective agent for targeting neo-lymphangiogenesis to inhibit lymphangiogenesis, by downregulating the expression of VEGF-C and VEGF-D.
5. Norcantharidin enhances TIMP‑2 antitumor and anti‑VM activities in GBCs through downregulating MMP‑2 and MT1‑MMP.
|Targets:||MMP(e.g.TIMP) | VEGFR | PKC | Wnt/β-catenin | Caspase | Bcl-2/Bax | DNA/RNA Synthesis | p53|
|Source:||The polypides of Mylabris phalerata Pallas|
|Solvent:||Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.|
|Storage:||Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C).
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.
Need more advice on solubility, usage and handling? Please email to: email@example.com
|After receiving:||The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.|
|1 mg||5 mg||10 mg||20 mg||25 mg|
|1 mM||5.9471 mL||29.7354 mL||59.4707 mL||118.9414 mL||148.6768 mL|
|5 mM||1.1894 mL||5.9471 mL||11.8941 mL||23.7883 mL||29.7354 mL|
|10 mM||0.5947 mL||2.9735 mL||5.9471 mL||11.8941 mL||14.8677 mL|
|50 mM||0.1189 mL||0.5947 mL||1.1894 mL||2.3788 mL||2.9735 mL|
|100 mM||0.0595 mL||0.2974 mL||0.5947 mL||1.1894 mL||1.4868 mL|
Int J Oncol. 2015 Feb;46(2):627-40.
|Norcantharidin enhances TIMP‑2 anti‑vasculogenic mimicry activity for human gallbladder cancers through downregulating MMP‑2 and MT1‑MMP.[Pubmed: 25405519]|
|Vasculogenic mimicry (VM) is a tumor microcirculation pattern in highly aggressive gallbladder cancers (GBCs). We recently reported the anti‑VM activity of Norcantharidin (NCTD) in highly aggressive GBC‑SD cells and xenografts. In this study, we further investigated that Norcantharidin enhanced tissue inhibitor of matrix metalloproteinase‑2 (TIMP‑2) anti‑VM activity for GBCs and the underlying mechanisms. In vivo and in vitro experiments were performed to determine the effects of Norcantharidin in combination with TIMP‑2 on tumor growth, host survival, VM formation, hemodynamic of GBC‑SD xenografts, and VM‑like networks and malignant phenotypes of GBC‑SD cells. Expression of matrix metalloproteinase (MMP)‑2 and membrane type 1‑MMP (MT1‑MMP) among human GBCs, GBC‑SD cells and xenografts were determined, respectively. The results showed that expression of MMP‑2 and MT1‑MMP in human GBCs, GBC‑SD cells and xenografts was significantly related to VM in GBCs; a shorter survival time of VM‑positive patients with high expression of MMP‑2 or MT1‑MMP compared to that of the patients with low expression. After treatment with Norcantharidin +TIMP‑2, tumor growth, VM formation, VM hemodynamic of the xenografts in vivo were significantly inhibited as compared to control, Norcantharidin or TIMP‑2 group, with a prolonged survival time of the xenograft mice (log‑rank test, P=0.0115); and these observations were confirmed by VM‑like networks by 3‑D matrices and showed that proliferation, apoptosis, invasion, migration of GBC‑SD cells in vitro were markedly affected. Furthermore, expression of MMP‑2 and MT1‑MMP in VM formation of the xenografts in vivo and GBC‑SD cells in vitro was downregulated as compared to control, Norcantharidin or TIMP‑2 group. Thus, we concluded that Norcantharidin enhances TIMP‑2 antitumor and anti‑VM activities in GBCs through downregulating MMP‑2 and MT1‑MMP.|
|Norcantharidin inhibits lymphangiogenesis by downregulating the expression of VEGF-C and VEGF-D in human dermal lymphatic endothelial cells in vitro.[Pubmed: 25572616]|
|AIMS: To investigate the effects of Norcantharidin on the growth and migration of human dermal lymphatic endothelial cells (HDLECs) and further characterize its effect on lymphangiogenesis. METHODS: A 3-dimensional fibrin gel lymphangiogenesis model was built. Flow cytometry was used to analyze the rate of apoptosis and necrosis. RT-PCR, immunohistochemistry and immunoblotting assays were used to examine the effect of Norcantharidin on vascular endothelial growth factor C (VEGF-C), VEGF-D and VEGF receptor 3 during in vitro lymphangiogenesis. RESULTS: Norcantharidin caused a marked dose and time-dependent inhibition of the growth of HDLECs with an IC50 of 40 nmol/l. The apoptotic rate of HDLECs was 13.21 ± 1.60% 24 h after treatment with 7.5 nmol/l Norcantharidin and 42.34 ± 3.80% with 90 nmol/l Norcantharidin (p < 0.01 vs. controls in both). Fibrin gel assays showed that Norcantharidin (15 nmol/l) reduced the number of tubular structures from 68.4 ± 5.2 in untreated controls to 10.9 ± 2.3 (p = 0.000). RT-PCR, immunohistochemistry and immunoblotting assays showed Norcantharidin markedly reduced the expression of VEGF-C and VEGF-D. CONCLUSION: Norcantharidin inhibits lymphangiogenesis by downregulating the expression of VEGF-C and VEGF-D, suggesting that Norcantharidin could be an effective agent for targeting neolymphangiogenesis.|
Oncol Lett. 2015 Feb;9(2):837-844. Epub 2014 Nov 19.
|Tamoxifen enhances the anticancer effect of cantharidin and norcantharidin in pancreatic cancer cell lines through inhibition of the protein kinase C signaling pathway.[Pubmed: 25624908]|
|Cantharidin is an active constituent of mylabris, a traditional Chinese therapeutic agent. Cantharidin is a potent and selective inhibitor of protein phosphatase 2A (PP2A). Cantharidin has been previously reported to efficiently repress the growth of pancreatic cancer cells. However, excessively activated protein kinase C (PKC) has been shown to improve cell survival following the adminstration of cantharidin. Tamoxifen is widely used in the treatment of estrogen receptor-positive breast cancer. In addition, an increasing number of studies have found that tamoxifen selectively inhibits PKC and represses growth in estrogen receptor-negative cancer cells. Administration of a combination of PKC inhibitor and PP2A inhibitors has been demonstrated to exert a synergistic anticancer effect. The proliferation of pancreatic cancer cells was analyzed by 3-(4,5-dimethyltiazol-2-yl]2, 5-diphenyltetrazo-lium bromide assay. The expression levels of ERα and ERβ in various pancreatic cancer cell lines were determined by reverse transcription polymerase chain reaction. In addition, the protein levels of PKCα and phosphorylated PKCα in pancreatic cell lines were analyzed by western blot analysis. In the present study, tamoxifen was found to exert a cytotoxic effect against pancreatic cancer cells independent of the hormone receptor status. Tamoxifen repressed the phosphorylation of PKC, and amplified the anticancer effect induced by cantharidin and Norcantharidin. The findings reveal a novel potential strategy against pancreatic cancer using co-treatment with tamoxifen plus cantharidin or cantharidin derivatives.|
Med Oncol. 2015 May;32(5):592.
|Norcantharidin inhibits Wnt signal pathway via promoter demethylation of WIF-1 in human non-small cell lung cancer.[Pubmed: 25814287]|
|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 Norcantharidin inhibited cell proliferation, induced apoptosis, arrested cell cycle and suppressed cell invasion/migration in vitro. Additionally, Wnt signal pathway transcription was also suppressed. Norcantharidin 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 Norcantharidin-treated groups compared with negative control (NC) groups. Abnormal methylation was observed in NC groups, while Norcantharidin treatment promoted WIF-1 demethylation. The present study revealed that Norcantharidin activated WIF-1 via promoter demethylation, inhibiting the canonical Wnt signal pathway in NSCLC, which may present a new therapeutic target in vivo.|
Cancer Lett. 2005 Jan 10;217(1):43-52.
|Norcantharidin-induced apoptosis in oral cancer cells is associated with an increase of proapoptotic to antiapoptotic protein ratio.[Pubmed: 15596295 ]|
|Norcantharidin (NCTD), the demethylated analogue of cantharidin, has been used to treat human cancers in China since 1984. It was recently found to be capable of inducing apoptosis in human colon carcinoma, hepatoma and glioblastoma cells by way of an elusive mechanism. In this study, we demonstrated that NCTD also induces apoptosis in human oral cancer cell lines SAS (p53 wild-type phenotype) and Ca9-22 (p53 mutant) as evidenced by nuclear condensation, TUNEL labeling, DNA fragmentation and cleavage of PARP. Apoptosis induced by NCTD was both dose- and time-dependent. We found NCTD did not induce Fas and FasL, implying that it activated other apoptosis pathways. Our data showed that NCTD caused accumulation of cytosolic cytochrome c and activation of caspase-9, suggesting that apoptosis occurred via the mitochondria mediated pathway. NCTD enhanced the expression of Bax in SAS cells consistent with their p53 status. Moreover, we showed that NCTD downregulated the expression of Bcl-2 in Ca9-22 and Bcl-XL in SAS. Our results suggest that NCTD-induced apoptosis in oral cancer cells may be mediated by an increase in the ratios of proapoptotic to antiapoptotic proteins. Since oral cancer cells with mutant p53 or elevated Bcl-XL levels showed resistance to multiple chemotherapeutic agents, NCTD may overcome the chemoresistance of these cells and provide potential new avenues for treatment.|
Eur J Cancer. 1995 Jun;31A(6):953-63.
|Effects of norcantharidin, a protein phosphatase type-2A inhibitor, on the growth of normal and malignant haemopoietic cells.[Pubmed: 7646929]|
|Cantharidin is a natural toxin that inhibits protein phosphatase type 2A (PP2A) and has antitumour effects in man. We have studied the synthetic analogue, Norcantharidin (NCTD), which has less nephrotoxic and phlogogenic side-effects, investigating the effects on the normal haemopoietic system and leukaemia cell growth. Daily intraperitoneal (i.p.) injection of NCTD induced dose and circadian time-dependent transient leucocytosis in normal mice, but did not accelerate bone marrow (BM) regeneration, or have haemopoietic offe-effects following chronic administration. NCTD stimulated the cell cycle progression of granulocyte-macrophage colony-forming cells (GM-CFC), stimulated DNA synthesis and increased the frequency of mitotic cells in short-term human BM cultures.|