The Fluoro-Thiazolylhydrazone Compound TSC-3C Inhibits Triple Negative Breast Cancer (TNBC) Cell Line Activity by
Jiajia Zhang1,2,3, Jiajia Dai4, Qingxuan Zheng4
1Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
Abstract:
Triple negative breast cancer (TNBC) is the most aggressive cancer in women, and despite improved treatments, it remains a major cause of morbidity and mortality. We and others have demonstrated that different hybrid compounds targeting PARP/MAPK or other pathways to inhibit cancer progression may lead to promising therapeutic results. We introduced fluorine to alter the physical properties of the compounds. TSC-3C was one of the generated compounds. Upon treatment with TSC-3C, MDA-MB-231 cell proliferation, invasion, and migration were inhibited. TSC-3C induced MDA-MB-231 cell mitochondrial dysfunction and apoptosis, which may be caused by reducing the level of phosphorylated p44/42 MAPK (ERK1/2) and increasing the level of p-JNK. The present study may help to elucidate the role of the MAPK pathway in the development of breast cancer and may promote further research on halogenated heterocyclic compounds for the treatment of breast cancer.
Insights
A novel compound, TSC-3C, effectively inhibits triple-negative breast cancer (TNBC) progression by inducing cell death and mitochondrial dysfunction. This research highlights potential new treatments for aggressive breast cancer by targeting the MAPK pathway.
Area of Science:
- Oncology
- Medicinal Chemistry
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options.
- Targeting multiple pathways, such as PARP and MAPK, shows promise for TNBC therapy.
- Fluorinated hybrid compounds are being explored for enhanced therapeutic properties.
Purpose of the Study:
- To evaluate the efficacy of a novel fluorinated hybrid compound, TSC-3C, against TNBC.
- To investigate the molecular mechanisms underlying TSC-3C's anti-cancer effects.
- To explore the role of the MAPK pathway in TNBC development and treatment.
Main Methods:
- Treatment of MDA-MB-231 TNBC cells with TSC-3C.
- Assessment of cell proliferation, invasion, and migration.
- Analysis of mitochondrial function and apoptosis induction.
- Evaluation of MAPK pathway signaling (ERK1/2 and JNK).
Main Results:
- TSC-3C significantly inhibited proliferation, invasion, and migration of MDA-MB-231 cells.
- TSC-3C induced mitochondrial dysfunction and apoptosis in TNBC cells.
- The compound altered MAPK signaling by reducing p-ERK1/2 and increasing p-JNK levels.
Conclusions:
- TSC-3C demonstrates potent anti-cancer activity against triple-negative breast cancer.
- The anti-cancer effects of TSC-3C are mediated through mitochondrial dysfunction, apoptosis, and modulation of the MAPK pathway.
- Halogenated heterocyclic compounds like TSC-3C represent a promising avenue for developing new TNBC therapies.
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