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  • Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models.

Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models.

Oncotarget (2016-10-27)
Petra Bullova, Antony Cougnoux, Luma Abunimer, Juraj Kopacek, Silvia Pastorekova, Karel Pacak
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-β-Tubulin antibody, Mouse monoclonal antibody produced in mouse, clone D66, purified from hybridoma cell culture
Sigma-Aldrich
Anti-SDHB antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution