Comparative evaluation of anti-angiogenic effects of noscapine derivatives

Abstract

Angiogenesis, the formation of new capillaries from pre-existing vessels, is essential for tumor progression. Synthetic derivatives of anti-cancer compound, noscapine (an opium alkaloid) such as Cl-noscapine, Br-noscapine and Folate-noscapine along with two of the reference compounds, TNP-470 and paclitaxel were examined for anti-angiogenic activities by using human umbilical vein endothelial cells (HUVECs). The noscapine derivatives showed anti-angiogenic activity albeit at high concentration compared to the reference compounds. All the tested compounds inhibited angiogenesis in a dose-dependent manner; the drug concentration causing 50% inhibition of cell survival was 11.87 μM for Cl-noscapine, 6.9 μM for Br-noscapine and 6.79 μM for folate-noscapine. Besides, all the noscapine derivatives significantly inhibited cord formation (IC50 for Cl-noscapine is 50.76 μM, for Br-noscapine is 90.08 μM and for folate-noscapine is 18.44 μM) as well as migration and invasion (IC50 value of Cl-noscapine is 28.01 μM, for Br-noscapine is 19.78 μM and for folate-noscapine is 10.76 μM) of endothelial cells. Based on these results, we speculated that the inhibitory effects on human endothelial cell proliferation of noscapine derivatives might be important for anti-angiogenesis.

Noscapine, an Emerging Medication for Different Diseases: A Mechanistic Review

“…Studies have shown that all noscapine derivatives showed dose-dependent antiangiogenic activity after 72 hours of treatment than those that did not receive noscapine [ 116 ]. According to the National Cancer Institute (NCI), IC 50 > 20, 6.9 µ M for Br-noscapine, and 6.79 µ M for folate-noscapine can inhibit VEGF ( Table 2 ) [ 117 ].…”

“…Thus, noscapine has anti-inflammatory, antiangiogenesis, and antimetastatic effects. In addition, examination of hypoxia conditions in human glioma cells has shown that noscapine has an inhibitory effect on VEGF, inhibits angiogenesis, and inhibits TNF- α and NF- κ B [ 116 ].…”

Structure of Papaver somniferum O-Methyltransferase 1 Reveals Initiation of Noscapine Biosynthesis with Implications for Plant Natural Product Methylation

“…Understanding how the, necessarily exquisite, acceptor specificity is achieved will be central to both enzyme and system-wide engineering campaigns to understand, modify, and exploit plant secondary metabolism. As noscapine-derived and inspired compounds become increasingly important as therapeutic agents (for recent examples, see refs and ) and in light of breakthroughs in the biosynthesis of noscapine in heterologous hosts systems, we believe the dissection of PSMT1 reported here is an important step toward the goal of being able to predict substrate specificity of the growing number of methyltransferase genes in the public domain that will ultimately contribute to their exploitation in rational engineering of natural products.…”

A review of research progress of antitumor drugs based on tubulin targets

“…For example, nosine and it analogs have been shown to have no sign of neurotoxicity or immunosuppression in ovarian cancer studies research. On the other hand, noscapine has been demonstrated to have neuroprotective effects in neurodegenerative disease and stroke mouse models ( 62 ). Concerning its anti-tumor effect on human prostate cancer cell lines LNCaP and PC-3, it was found that the joint application of paclitaxel and nicardipine can increase the percentage of apoptotic cells.…”