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

  • Meric A. AltinozEmail author
  • Gulacti Topcu
  • Ahmet Hacimuftuoglu
  • Alp Ozpinar
  • Aysel Ozpinar
  • Emily Hacker
  • İlhan Elmaci
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 Lettré 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-κB, 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.

Keywords

Noscapine Microtubule Glial tumor Glioblastoma 

Notes

Compliance with Ethical Standards

Conflict of interest

All the authors declared that thy have no conflict of interest.

Research Involving Human Participants and/or Animals

This study does not involve any human participants and/or animals.

Informed Consent

As this study does not involve any human subjects, informed consents were not needed.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medical BiochemistryAcibadem UniversityIstanbulTurkey
  2. 2.Department of PsychiatryMaastricht UniversityMaastrichtThe Netherlands
  3. 3.Department of PharmacyBezmi Alem UniversityIstanbulTurkey
  4. 4.Department of Medical PharmacologyErzurum Ataturk UniversityErzurumTurkey
  5. 5.Department of NeurosurgeryUniversity of PittsburghPittsburghUSA
  6. 6.Department of NeurosurgeryAcibadem HospitalIstanbulTurkey

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