Noscapine, a Non-addictive Opioid and Microtubule-Inhibitor in Potential Treatment of Glioblastoma

Meric A. Altinoz*, Gulacti Topcu, Ahmet Hacimuftuoglu, Alp Ozpinar, Aysel Ozpinar, Emily Hacker, Ilhan Elmaci

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

Abstract

Noscapine is a phthalide isoquinoline alkaloid that easily traverses the blood brain barrier and has been used for years as an antitussive agent with high safety. Despite binding opioid receptors, noscapine lacks significant hypnotic and euphoric effects rendering it safe in terms of addictive potential. In 1954, Hans Lettre first described noscapine as a mitotic poison. The drug was later tested for cancer treatment in the early 1960's, yet no effect was observed likely as a result of its short biological half-life and limited water solubility. Since 1998, it has regained interest thanks to studies from Emory University, which showed its anticancer activity in animal models with negligible toxicity. In contrast to other microtubule-inhibitors, noscapine does not affect the total intracellular tubulin polymer mass. Instead, it forces the microtubules to spend an increased amount of time in a paused state leading to arrest in mitosis and subsequently inducing mitotic slippage/mitotic catastrophe/apoptosis. In experimental models, noscapine does not induce peripheral neuropathy, which is common with other microtubule inhibitors. Noscapine also inhibits tumor growth and enhances cancer chemosensitivity via selective blockage of NF-kappa B, an important transcription factor in glioblastoma pathogenesis. Due to their anticancer activities and high penetration through the blood-brain barrier, noscapine analogues strongly deserve further study in various animal models of glioblastoma as potential candidates for future patient therapy.

Original languageEnglish
Pages (from-to)1796-1806
Number of pages11
JournalNeurochemical Research
Volume44
Issue number8
DOIs
Publication statusPublished - Aug 2019

Keywords

  • Noscapine
  • Microtubule
  • Glial tumor
  • Glioblastoma
  • CEREBROSPINAL-FLUID
  • GLIOMA-CELLS
  • IN-VITRO
  • CANCER
  • BRAIN
  • APOPTOSIS
  • AGENT
  • PROLIFERATION
  • INVASION
  • BINDING

Fingerprint

Dive into the research topics of 'Noscapine, a Non-addictive Opioid and Microtubule-Inhibitor in Potential Treatment of Glioblastoma'. Together they form a unique fingerprint.

Cite this