Metabolic Modulation by Dimethyl Fumarate Alters Docetaxel Responses in Prostate Cancer Cells

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Dimethyl fumarate (DMF) is an approved drug with potential for cancer treatment.
• Docetaxel (DCT) is a standard chemotherapy agent for prostate cancer.

Purpose of the Study:

• To investigate the combined effects of low-dose DMF and DCT on prostate cancer cells.
• To explore the underlying mechanisms of DMF-DCT interaction in cancer cells.

Main Methods:

• Prostate cancer cell lines (PC-3, LNCaP) and normal cells (RWPE-1) were treated with DMF and DCT.
• Evaluated cell viability, apoptosis, oxidative stress, mitochondrial function, and metabolic parameters (glucose, lactate).
• Assessed gene expression of LDHA and SOD2.

Main Results:

• DMF and DCT combination exhibited dose- and ratio-dependent cytotoxicity in cancer cells, with minimal toxicity in normal cells.
• DMF-DCT treatment induced apoptosis, oxidative stress, and mitochondrial dysfunction in LNCaP cells.
• PC-3 cells showed enhanced sensitivity to the combination, with a docetaxel dose-sparing effect and metabolic alterations.

Conclusions:

• DMF acts as a context-dependent metabolic modulator of docetaxel response in prostate cancer.
• The DMF-DCT combination warrants further investigation as a potential therapeutic strategy for prostate cancer.