Noscapine: from cough syrup to cancer

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Noscapine is a phthalide isoquinoline non-narcotic alkaloid derived from the opium poppy Papaver somniferum, with mild analgesic, antitussive, and potential antineoplastic activities. Noscapine exerts its antitussive effects through the activation of sigma opioid receptors. This agent appears to exert its antimitotic effect by binding to tubulin, resulting in a disruption of microtubule assembly dynamics and subsequently, the inhibition of mitosis and tumor cell death.

Here’s another mild compound that has been in use for quite some time and could be re-purposed as a cancer fighting drug, particularly in a cocktail approach. Its anti-mitotic properties would come in quite handy. As usual follow the links to find out what this compound offers.

A Safe Cough Suppressant with Newly Discovered Effects in Treating Cancer and Stroke

Microtubules, leukemia, and cough syrup

Study Shows That A Cough Medicine Ingredient Could Effectively Treat Prostate Cancer

Noscapine and Its Analogues as Anti-Cancer Agents

Antitumor Activity of Noscapine in Combination with Doxorubicin in Triple Negative Breast Cancer

Noscapine, a benzylisoquinoline alkaloid, sensitizes leukemic cells to chemotherapeutic agents and cytokines by modulating the NF-κB signaling pathway

Noscapine Induced Apoptosis via Downregulation of Survivin in Human Neuroblastoma Cells Having Wild Type or Null p53

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Auranofin (aka Ridaura) : An FDA approved anti-rheumatic drug that induces oxidative stress and apoptosis in CLL cells

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“By inhibiting thioredoxin reductase activity and increasing intracellular reactive oxygen species levels, auranofin induced a lethal endoplasmic reticulum stress response in cultured and primary CLL cells. In addition, auranofin displayed synergistic lethality with heme oxygenase-1 and glutamate-cysteine ligase inhibitors against CLL cells. Auranofin overcame apoptosis resistance mediated by protective stromal cells, and it also killed primary CLL cells with deletion of chromosome 11q or 17p. In TCL-1 transgenic mice, an in vivo model of CLL, auranofin treatment markedly reduced tumor cell burden and improved mouse survival. Our results provide a rationale to reposition the approved drug auranofin for clinical evaluation in the therapy of CLL”.

Auranofin Induces Lethal Oxidative and Endoplasmic Reticulum Stress and Exerts Potent Preclinical Activity against Chronic Lymphocytic Leukemia

Auranofin Induces a Reversible In-Vivo Stress Response That Correlates With a Transient Clinical Effect In Patients With Chronic Lymphocytic Leukemia

Effect of auranofin on oxidative and endoplasmic reticulum stress as well as anti-CLL activity with proteasome inhibitor

Targeting the Redox System to Overcome Mechanisms of Drug Resistance in Chronic Lymphocytic Leukemia

Phase I and II Study of Auranofin in Chronic Lymphocytic Leukemia (CLL)

New NIH Center Broadens Scope of Translational Research

Nearly 30 years after auranofin gained approval from the U.S. Food and Drug Administration to treat rheumatoid arthritis, researchers are repurposing the drug for a possible new use: chronic lymphocytic leukemia (CLL). Moreover, the arthritis drug could emerge as a model for accelerating patients’ access to other repurposed drugs or for rescuing drugs that the pharmaceutical industry has abandoned and now are languishing on companies’ shelves, researchers say.

“What we did was go from in vitro experiments directly into patients,” said Scott Weir, Pharm.D., Ph.D., director of the Institute for Advancing Medical Innovation at the University of Kansas Medical Center, one of several test sites nationwide, which soon will include the National Heart, Lung, and Blood Institute.

“We didn’t feel we needed to go through the traditional drug paradigm,” he said, given auranofin’s earlier testing for safety and efficacy.

As a result, less than 2 years after scientists discovered that auranofin could kill CLL cells in the lab, researchers began dosing the first relapsed CLL patient in a clinical trial. That compares with, on average, 8–10 years to reach a similar stage in drug development for a new drug, according to Weir, one of several authors of a recent commentary in Cancer Research about the pilot project.

The repurposing of older drugs such as auranofin, as well as second looks at unapproved agents stuck in the regulatory pipeline, is part of an intense systematic approach to translational research embodied in the first new center at the National Institutes of Health in more than a decade. The National Center for Advancing Translational Sciences (NCATS), which replaced the National Center for Research Resources earlier this year, incorporates many of the former center’s programs.