Piperlongumine: a natural plant-based compound that is selectively cytotoxic to cancer cells

Updated with more research links and a source for piperlongumine! This natural compound is apparently effective against so many different cancer types. I’ve only included links to the free research articles, but there are many more behind the paywalls!

Scientists at the Broad Institute and Massachusetts General Hospital (MGH) have discovered a novel compound that blocks this response to oxidative stress selectively in cancer cells but spares normal cells, with an effectiveness that surpassed a chemotherapy drug currently used to treat breast cancer. Their findings, based on experiments in cell culture and in mice, appear online in Nature on July 13.

The plant-based compound piperlongumine (PL), derived from the fruit of a pepper plant found in southern India and southeast Asia, appears to kill cancer cells by jamming the machinery that dissipates high oxidative stress and the resulting ROS. Normal cells have low levels of ROS, in tune with their more modest metabolism, so they don’t need high levels of the anti-oxidant enzymes that PL stymies once they pass a certain threshold.

Taking out a cancer’s co-dependency:
Novel compound selectively kills cancer cells by blocking their response to oxidative stress

Redox-directed cancer therapeutics: Taurolidine and Piperlongumine as broadly effective antineoplastic agents (Review)

Synthesis, cellular evaluation, and mechanism of action of piperlongumine analogs

Selective killing of cancer cells by a small molecule targeting the stress response to ROS

Piperlongumine Induces Apoptosis and Synergizes with Cisplatin or Paclitaxel in Human Ovarian Cancer Cells

Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer

Targeting Aberrant Glutathione Metabolism to Eradicate Human Acute Myelogenous Leukemia Cells

Piperlongumine combined with vitamin C as a new adjuvant therapy against gastric cancer regulates the ROS–STAT3 pathway

Piperlongumine Induces Cell Cycle Arrest via Reactive Oxygen Species Accumulation and IKKβ Suppression in Human Breast Cancer Cells

Piperlongumine, a piper alkaloid targets Ras/PI3K/Akt/mTOR signaling axis to inhibit tumor cell growth and proliferation in DMH/DSS induced experimental colon cancer

Piperlongumine induces apoptotic and autophagic death of the primary myeloid leukemia cells from patients via activation of ROS-p38/JNK pathways

Inhibition of cancer growth in vitro and in vivo by a novel ROS-modulating agent with ability to eliminate stem-like cancer cells

New Mild and Simple Approach to Isothiocyanates: A Class of Potent Anticancer Agents

Targeting p53-deficient chronic lymphocytic leukemia cells in vitro and in vivo by ROS-mediated mechanism

Effective elimination of chronic lymphocytic leukemia cells in the stromal microenvironment by a novel drug combination strategy using redox-mediated mechanisms

Long Pepper 500mg/Capsule – Piperlongumine

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

“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.