Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

Area of Science:

• Oncology
• Cell Biology
• Metabolomics

Background:

• Colorectal cancer (CRC) progression mechanisms require elucidation for effective prevention strategies.
• Dietary metabolite delta-Valerobetaine (δVB) exhibits cytotoxic effects on colon cancer cells through autophagy and apoptosis.
• Understanding δVB's precise mechanism in colon cancer cell death is crucial.

Purpose of the Study:

• To investigate the apoptotic cascade and mitochondrial dysfunction mechanisms underlying δVB-induced colon cancer cell death.
• To evaluate the role of specific molecular players, including the PINK1/Parkin pathway, in δVB's effects.
• To deepen knowledge on δVB's impact on colorectal adenocarcinoma cell lines (SW480 and SW620).

Main Methods:

• Assessing δVB's effect on cell viability and cell cycle progression in SW480 and SW620 cells.
• Analyzing caspase-3 activation, mitochondrial membrane potential, and SIRT3 levels.
• Evaluating protein expression of PINK1, Parkin, and LC3B to understand mitophagy involvement.

Main Results:

• δVB reduced cell viability in a time-dependent manner, with IC50 at 72 h (1.5 mM).
• δVB induced G2/M cell cycle arrest, increased caspase-3 activation, and decreased mitochondrial membrane potential.
• Upregulation of PINK1, Parkin, and LC3B confirmed the activation of PINK1/Parkin-mediated mitophagy.

Conclusions:

• δVB induces colon cancer cell death via apoptosis, involving caspase-3 activation and mitochondrial dysfunction.
• The PINK1/Parkin pathway and mitophagy play a critical role in δVB-induced mitochondrial dysfunction and apoptosis.
• Findings support δVB's potential role in targeting colorectal cancer progression through mitochondrial-mediated cell death pathways.