Article Publish Status: FREE
Abstract Title:

Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models.

Abstract Source:

Oncotarget. 2016 May 26. Epub 2016 May 26. PMID: 27244895

Abstract Author(s):

Petra Bullova, Antony Cougnoux, Luma Abunimer, Juraj Kopacek, Silvia Pastorekova, Karel Pacak

Article Affiliation:

Petra Bullova

Abstract:

Hypoxia is a common feature of solid tumors that activates a plethora of pathways, resulting in proliferation and resistance of cancer cells to radio- and chemotherapy. Pheochromocytomas/paragangliomas (PHEOs/PGLs) with mutations in the gene coding for the subunit B of succinate dehydrogenase (SDHB) are the most aggressive forms of the disease, which is partially due to their pseudohypoxic character, metabolic abnormalities, and elevated reactive oxygen species (ROS) levels. We investigated the effect of piperlongumine (PL), a natural product with cytotoxic properties restricted to cancer cells by significantly increasing intracellular ROS levels, on PHEO cells. Here we report for the first time that PL mediates PHEO cell death by activating both apoptosis and necroptosis in vitro and in vivo. This effect is magnified in hypoxic conditions, making PL a promising potential candidate for use as a therapeutic option for patients with PHEO/PGL, including those with SDHB mutations.

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