Abstract
Cancer stem cells are contributors of chemotherapeutic resistance. We have previously shown that resveratrol (RSV) potentiates grape seed extract (GSE) induced apoptosis and suppression of proliferation in human colon cancer cell lines, but not in normal colonocytes, via p53 dependent mitochondrial apoptotic pathway. However, no information is available on whether grape compounds elevate apoptosis in the cancer stem cells. We hypothesized that RSV‐GSE combination will elevate apoptosis in human colon cancer stem cells (CD34+, CD44+, CD133+, ALDH1b1+), even the presence of IGF‐1 (a mitogen growth factor elevated during obesity), via elevation of p53 dependent pathway. RSV‐GSE combination elevated (p<0.05) apoptosis (Caspase 3/7 Glo and TUNEL assay) in the colon cancer stem cell line similar to that of 5‐fluorouracil (5‐FU), a standard colon cancer chemotherapeutic drug. P53 inhibition by pithifrin‐α (150 μM), a transcriptional inhibitor, and p53 shRNA (2 × 105 lentiviral particles) suppressed (p<0.05) RSV‐GSE and 5‐fluorouracil induced apoptosis. RSV‐GSE elevated (p<0.05) apoptosis, even in the presence of IGF‐1, indicating its potential efficacy in obese condition. This study demonstrates RSV‐GSE induced apoptosis in colon cancer stem cells via p53 dependent pathway. Results suggest that consumption of RSV‐GSE could contribute towards colon cancer prevention.
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