Publication Date
5-24-2022
Journal
Communications Biology
DOI
10.1038/s42003-022-03413-w
PMID
35610507
PMCID
PMC9130234
PubMedCentral® Posted Date
5-24-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Animals, Breast Neoplasms, DNA, DNA Repair, Female, Humans, Mice, Receptors, Estrogen
Abstract
The major limitations of DNA-targeting chemotherapy drugs include life-threatening toxicity, acquired resistance and occurrence of secondary cancers. Here, we report a small molecule, Carbazole Blue (CB), that binds to DNA and inhibits cancer growth and metastasis by targeting DNA-related processes that tumor cells use but not the normal cells. We show that CB inhibits the expression of pro-tumorigenic genes that promote unchecked replication and aberrant DNA repair that cancer cells get addicted to survive. In contrast to chemotherapy drugs, systemic delivery of CB suppressed breast cancer growth and metastasis with no toxicity in pre-clinical mouse models. Using PDX and ex vivo explants from estrogen receptor (ER) positive, ER mutant and TNBC patients, we further demonstrated that CB effectively blocks therapy-sensitive and therapy-resistant breast cancer growth without affecting normal breast tissue. Our data provide a strong rationale to develop CB as a viable therapeutic for treating breast cancers.
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Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Medical Sciences Commons, Obstetrics and Gynecology Commons
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