Dr. Weeks’ Comment: In this important animal study, 50 mice with colon cancer were separated into three groups – a control group that received no treatment, a group that received an anti-inflammatory drug (sulindac) and a group which were given grape compounds including grape seeds and their extracts. The results reinforce the truism that the whole seed as prepared in nature is more powerful than a drug. In this case not only did the grape sees kill cancer STEM cells but eating the grape seed was 50% more beneficial than taking the synthetic drug.
“…RSV-GSE also induced mitochondrial-mediated apoptosis in colon CSCs…”
BMC Complement Altern Med. 2016 Aug 9;16:278. doi: 10.1186/s12906-016-1254-2.
Grape compounds suppress colon cancer stem cells in vitro and in a rodent model of colon carcinogenesis.
Reddivari L1, Charepalli V2, Radhakrishnan S2, Vadde R2,3, Elias RJ2, Lambert JD2,4, Vanamala JK5,6,7.
Abstract
BACKGROUND:
We have previously shown that the grape bioactive compound resveratrol (RSV) potentiates grape seed extract (GSE)-induced colon cancer cell apoptosis at physiologically relevant concentrations. However, RSV-GSE combination efficacy against colon cancer stem cells (CSCs), which play a key role in chemotherapy and radiation resistance, is not known.
METHODS:
We tested the anti-cancer efficacy of the RSV-GSE against colon CSCs using isolated human colon CSCs in vitro and an azoxymethane-induced mouse model of colon carcinogenesis in vivo.
RESULTS:
RSV-GSE suppressed tumor incidence similar to sulindac, without any gastrointestinal toxicity. Additionally, RSV-GSE treatment reduced the number of crypts containing cells with nuclear β-catenin (an indicator of colon CSCs) via induction of apoptosis. In vitro, RSV-GSE suppressed – proliferation, sphere formation, nuclear translocation of β-catenin (a critical regulator of CSC proliferation) similar to sulindac in isolated human colon CSCs.
RSV-GSE, but not sulindac, suppressed downstream protein levels of Wnt/β-catenin pathway, c-Myc and cyclin D1.
RSV-GSE also induced mitochondrial-mediated apoptosis in colon CSCs characterized by elevated p53, Bax/Bcl-2 ratio and cleaved PARP.
Furthermore, shRNA-mediated knockdown of p53, a tumor suppressor gene, in colon CSCs did not alter efficacy of RSV-GSE.
CONCLUSION:
The suppression of Wnt/β-catenin signaling and elevated mitochondrial-mediated apoptosis in colon CSCs support potential clinical testing/application of grape bioactives for colon cancer prevention and/or therapy.