The PI3K/Akt pathway is involved in procyanidin-mediated suppression of human colorectal cancer cell growth

Molecular Carcinogenesis
Ying Yng ChoyPatricia I Oteiza

Abstract

Colorectal cancer (CRC) has the third highest incidence worldwide. Epidemiological studies showed that the consumption of fruit and vegetables containing procyanidins (PCA), polymers of flavan-3-ols, is associated with lower CRC risk. However, the molecular mechanisms supporting this positive association are unclear. This study investigated the capacity of PCA with different degrees of polymerization to reduce CRC cell growth, characterizing the underlying mechanisms. Compared to the monomer ((-)-epicatechin) and the trimer, the hexamer (Hex) was the most active at reducing CRC cell viability. Hex caused a concentration- (2.5-50 μM) and time- (24-72 h) dependent decrease in the viability of six human CRC cell lines in culture. Hex caused CRC apoptotic Caco-2 cell death within 24 h, as evidenced by caspase 3 and caspase 9 activation, DNA fragmentation, and changes in nuclear morphology/staining. Hex-induced apoptosis occurs through the mitochondrial pathway, as evidenced by an increased Bad mitochondrial translocation, and cytochrome c release from the mitochondria to the cytosol. Hex also arrested the Caco-2 cell cycle at G2 /M phase and upregulated genes involved in autophagy. Mechanistically, in Caco-2 cells Hex inhibited the...Continue Reading

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Aug 25, 2016·Nutrients·Yue ZhouHua-Bin Li
Dec 23, 2016·Medicinal Research Reviews·Yuee CaiMeiwan Chen
Nov 26, 2019·Food Science & Nutrition·Muhammad Sajid ArshadHafiza Rehana
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Feb 9, 2018·Molecular Aspects of Medicine·Cesar G FragaMonica Galleano

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