Thiosemicarbazide Derivatives Targeting Human TopoIIα and IDO-1 as Small-Molecule Drug Candidates for Breast Cancer Treatment

International Journal of Molecular Sciences · 5 authors, 3 centres

AI SUMMARY

FIDELITY 100%

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

This preclinical study tested three thiosemicarbazide derivatives on breast cancer cell lines and found they selectively inhibit cancer cell growth, induce apoptosis and cell cycle arrest, and inhibit drug-resistance transporters, while showing preliminary safety.

Full summary

1,062 CHARS

The study evaluated the anticancer effects of three thiosemicarbazide derivatives (compounds 1–3) in MCF-7 (ER/PR-positive) and MDA-MB-231 (triple-negative) breast cancer cell lines in vitro. The compounds selectively suppressed cancer cell growth with selectivity indexes up to 5.6 compared to normal breast epithelial cells (MCF-10A). They promoted apoptosis via caspase-8 and caspase-9 pathways and caused dose-dependent S-phase cell cycle arrest. The compounds also dose-dependently inhibited the activity of ABC transporters (MDR1, MRP1/2, BCRP), which are linked to chemoresistance. Compound 1 induced autophagy, but its role in cell death requires further study. Preliminary ADME-Tox tests showed no direct hemolytic activity and no significant inhibition of CYP3A4 or CYP2D6 enzymes. Limitations include the preclinical, in vitro nature of the study and that immune-mediated hemolytic effects could not be assessed. The findings suggest these dual topoIIα/IDO-1 inhibitors have potential as breast cancer drug candidates warranting further investigation.

STUDY TYPE

other

SPECIALTY

oncology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10051798

Thiosemicarbazide Derivatives Targeting Human TopoIIα and IDO-1 as Small-Molecule Drug Candidates for Breast Cancer Treatment

International Journal of Molecular Sciences

READ THE FULL PAPER

ABSTRACT

In 2020, breast cancer became the most frequently diagnosed type of cancer, with nearly 2.3 million new cases diagnosed. However, with early diagnosis and proper treatment, breast cancer has a good prognosis. Here, we investigated the effect of thiosemicarbazide derivatives, previously identified as dual inhibitors targeting topoisomerase IIα and indoleamine-2,3-dioxygenase 1 (IDO 1), on two distinct types of breast cancer cells (MCF-7 and MDA-MB-231). The investigated compounds ( 1 – 3 ) selectively suppressed the growth of breast cancer cells and promoted apoptosis via caspase-8- and caspase-9-related pathways. Moreover, these compounds caused S-phase cell cycle arrest and dose-dependently inhibited the activity of ATP-binding cassette transporters (MDR1, MRP1/2 and BCRP) in MCF-7 and MDA-MB-231 cells. Additionally, following incubation with compound 1, an increased number of autophagic cells within both types of the investigated breast cancer cells was observed. During preliminary testing of ADME-Tox properties, the possible hemolytic activities of compounds 1 – 3 and their effects on specific cytochrome P450 enzymes were evaluated.

CITATION EXPORT

Barbara Kaproń, Robert Czarnomysy, Dominika Radomska et al.. Thiosemicarbazide Derivatives Targeting Human TopoIIα and IDO-1 as Small-Molecule Drug Candidates for Breast Cancer Treatment. International Journal of Molecular Sciences. (2023). https://doi.org/10.3390/ijms24065812

AUTHORS

5 · 3 CENTRES

Barbara Kaproń, Robert Czarnomysy, Dominika Radomska, Krzysztof Bielawski, Tomasz Plech

1Department of Clinical Genetics, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
2Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilińskiego 1, 15-089 Białystok, Poland
3Department of Pharmacology, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland

EDITOR / REVIEWER

Francisco Estevez