Autocrine Motility Factor and Its Peptide Derivative Inhibit Triple-Negative Breast Cancer by Regulating Wound Repair, Survival, and Drug Efflux

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Nov 9

PMID 39519266

Authors

Se Gie Kim

Seok Joong Kim

Thanh Van Duong

Yuhan Cho

Bogeun Park

Ulhas Sopanrao Kadam

Hee Sung Park

Jong Chan Hong

Affiliations

Soon will be listed here.

Abstract

Triple-negative breast cancer (TNBC) presents a significant challenge in oncology due to its aggressive nature and limited targeted therapeutic options. This study explores the potential of autocrine motility factor (AMF) and an AMF-derived peptide as novel treatments for TNBC. AMF, primarily secreted by neoplastic cells, plays a crucial role in cancer cell motility, metastasis, and proliferation. The research demonstrates that AMF and its derived peptide inhibit TNBC cell proliferation by modulating cellular migration, redox homeostasis, apoptotic pathways, and drug efflux mechanisms. Dose-dependent antiproliferative effects were observed across three TNBC cell lines, with higher concentrations impairing cellular migration. Mechanistic studies revealed decreased glucose-6-phosphate dehydrogenase expression and elevated reactive oxygen species production, suggesting redox imbalance as a primary mediator of apoptosis. Combination studies with conventional therapeutics showed near-complete eradication of resistant TNBC cells. The observed reduction in p53 levels and increased intranuclear doxorubicin accumulation highlight the AMF/AMF peptide's potential as multidrug resistance modulators. This study underscores the promise of using AMF/AMF peptide as a novel therapeutic approach for TNBC, addressing current treatment limitations and warranting further investigation.

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