Combination of Low-Dose Sulforaphane and Docetaxel on Mitochondrial Function and Metabolic Reprogramming in Prostate...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Monotherapies for prostate cancer face limitations due to chemoresistance and adverse effects.
• Docetaxel (DCT) is a standard chemotherapy agent, but its efficacy can be limited by resistance and toxicity.
• Sulforaphane (SFN), a natural compound, has shown potential anticancer properties.

Purpose of the Study:

• To investigate the therapeutic efficacy of combining low-dose sulforaphane (SFN) with docetaxel (DCT) in prostate cancer.
• To evaluate the impact of the SFN:DCT combination on metabolic markers and cell viability in prostate cancer cell lines.
• To determine if the combination therapy can achieve comparable efficacy to monotherapy at reduced doses.

Main Methods:

• Prostate cancer cell lines (LNCaP and PC-3) were treated with SFN and DCT at various concentrations.
• Cell viability was assessed, along with metabolic markers including glucose consumption, lactate production, reactive oxygen species (ROS), mitochondrial mass, and caspase activity.
• The SFN:DCT combination was tested at half-reduced IC50 values.

Main Results:

• In LNCaP cells, the SFN:DCT combination reduced cell viability similarly to DCT monotherapy (50% vs. 48%) and increased caspase 3 activation.
• In PC-3 cells, the SFN:DCT combination induced caspase 3 activation and significantly reduced mitochondrial mass, indicating effectiveness against aggressive phenotypes.
• The combination therapy demonstrated comparable efficacy to DCT monotherapy at lower doses, suggesting a potential for reduced side effects.

Conclusions:

• The combination of sulforaphane and docetaxel is a promising strategy for early-stage prostate cancer treatment.
• Low-dose SFN:DCT therapy maintains therapeutic impact while potentially mitigating the adverse effects associated with conventional docetaxel treatment.
• Targeting metabolic vulnerabilities with SFN:DCT offers a novel approach for enhancing prostate cancer therapy.