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

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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.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Acibadem University, Istanbul, Turkey

    Meric A. Altinoz & Aysel Ozpinar

  2. Department of Psychiatry, Maastricht University, Maastricht, The Netherlands

    Meric A. Altinoz

  3. Department of Pharmacy, Bezmi Alem University, Istanbul, Turkey

    Gulacti Topcu

  4. Department of Medical Pharmacology, Erzurum Ataturk University, Erzurum, Turkey

    Ahmet Hacimuftuoglu

  5. Department of Neurosurgery, University of Pittsburgh, Pittsburgh, USA

    Alp Ozpinar & Emily Hacker

  6. Department of Neurosurgery, Acibadem Hospital, Istanbul, Turkey

    İlhan Elmaci

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Altinoz, M.A., Topcu, G., Hacimuftuoglu, A. et al. Noscapine, a Non-addictive Opioid and Microtubule-Inhibitor in Potential Treatment of Glioblastoma. Neurochem Res 44, 1796–1806 (2019). https://doi.org/10.1007/s11064-019-02837-x

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