Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 15, Pages -Publisher
MDPI
DOI: 10.3390/ijms22158117
Keywords
colon cancer; mitophagy; mitochondrial dysfunction; PINK1; Parkin
Funding
- VALERE 2019 Program University of Campania L. Vanvitelli [PON I&C 2014-2020-TABAREZO-F/200085/01-03/X45]
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This study aimed to deepen current knowledge on the mechanism of delta VB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that delta VB activated mitochondrial apoptosis through PINK1/Parkin pathways.
Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. delta-Valerobetaine (delta VB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of delta VB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that delta VB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with delta VB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that delta VB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by delta VB in SW480 and SW620 colon cancer cells.
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