Human pancreatic cancer cells under nutrient deprivation are vulnerable to redox system inhibition [Cell Biology]

In this study, we constructed a high-throughput screening system to identify such small molecules and screened chemical libraries and microbial culture extracts. We were able to determine that some small molecular compounds, such as penicillic acid, papyracillic acid, and auranofin, exhibit preferential cytotoxicity to human pancreatic cancer cells under nutrient-deprived compared with nutrient-sufficient conditions. Further analysis revealed that these compounds target to redox systems such as GSH and thioredoxin and induce accumulation of reactive oxygen species in nutrient-deprived cancer cells, potentially contributing to apoptosis under nutrient-deprived conditions. Nutrient-deficient cancer cells are often deficient in GSH; thus, they are susceptible to redox system inhibitors. Targeting redox systems might be an attractive therapeutic strategy under nutrient-deprived conditions of the tumor microenvironment.

Source: Journal of Biological Chemistry - December 4, 2020 Category: Chemistry Authors: Takefumi Onodera, Isao Momose, Hayamitsu Adachi, Yohko Yamazaki, Ryuichi Sawa, Shun-ichi Ohba, Manabu Kawada Tags: Metabolism Source Type: research