Global metabolic alterations in colorectal cancer cells during irinotecan-induced DNA replication stress.

ABSTRACT:

Background

Metabolic adaptations can allow cancer cells to survive DNA-damaging chemotherapy. This unmet clinical challenge is a potential vulnerability of cancer. Accordingly, there is an intense search for mechanisms that modulate cell metabolism during anti-tumor therapy. We set out to define how colorectal cancer CRC cells alter their metabolism upon DNA replication stress and whether this provides opportunities to eliminate such cells more efficiently.

Methods

We incubated p53-positive and p53-negative permanent CRC cells and short-term cultured primary CRC cells with the topoisomerase-1 inhibitor irinotecan and other drugs that cause DNA replication stress and consequently DNA damage. We analyzed pro-apoptotic mitochondrial membrane depolarization and cell death with f

SUBMITTER: Marx C 

PROVIDER: S-EPMC9251592 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature