ECE2019 Poster Presentations Thyroid 1 (70 abstracts)
Targeting the pentose phosphate pathway in thyroid cancer cells
Shih-Ping Cheng 1, , Chien-Liang Liu 1, , Jie-Jen Lee 1, , Yi-Chiung Hsu 3 & Shih-Yuan Huang 1
1MacKay Memorial Hospital, Taipei, Taiwan; 2Mackay Medical College, New Taipei City, Taiwan; 3National Central University, Taoyuan City, Taiwan.
The pentose phosphate pathway (PPP) plays an important role in the biosynthesis of ribonucleotide precursor ribose-5-phosphate and NADPH. Glycolytic reprogramming of cancer cells frequently involves dysregulation of PPP flux. A previous study suggested that the expression of transketolase like 1 (TKTL1) was associated with invasiveness of papillary thyroid cancer. In the present study, we found that the combination of G6PD and transketolase inhibitors exerted a synergic effect on cell growth inhibition in thyroid cancer cells. Furthermore, targeting PPP significantly increased cellular reactive oxygen species (ROS) and induced endoplasmic reticulum stress and apoptosis. Suppressed cell viability could be partially rescued with treatment with a ROS scavenger or apoptosis inhibitor but not the inhibitor of protein kinase R-like endoplasmic reticulum kinase. Taken together, PPP blockade leads to an impairment of NADPH production and causes ROS-mediated apoptosis in thyroid cancer cells.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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