Anthocyanin-containing purple-fleshed potatoes suppress colon tumorigenesis via elimination of colon cancer stem cells

• Published in: The Journal of nutritional biochemistry 2015-12, Vol.26 (12), p.1641-1649
• Main Authors: Charepalli, Venkata, Reddivari, Lavanya, Radhakrishnan, Sridhar, Vadde, Ramakrishna, Agarwal, Rajesh, Vanamala, Jairam K.P.
• Format: Article
• Language: English
• Subjects: Animals; Anthocyanins; Anthocyanins - chemistry; Antineoplastic Agents - chemistry; Apoptosis; Azoxymethane - chemistry; bcl-2-Associated X Protein - metabolism; beta Catenin - metabolism; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic - metabolism; Colon cancer stem cells; Colonic Neoplasms - diet therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - prevention & control; Cytochromes c - metabolism; Food; Humans; In Situ Nick-End Labeling; Lentivirus; Male; Mice; Mitochondria - metabolism; Neoplastic Stem Cells - cytology; Neoplastic Stem Cells - metabolism; p53; Purple-fleshed potatoes; RNA, Small Interfering - metabolism; Solanum tuberosum - chemistry; Sulindac - chemistry; Tumor Suppressor Protein p53 - metabolism; Wnt Proteins - metabolism; β-Catenin
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2015.08.005

Cancer stem cells (CSCs) are shown to be responsible for initiation and progression of tumors in a variety of cancers. We previously showed that anthocyanin-containing baked purple-fleshed potato (PP) extracts (PA) suppressed early and advanced human colon cancer cell proliferation and induced apoptosis, but their effect on colon CSCs is not known. Considering the evidence of bioactive compounds, such as anthocyanins, against cancers, there is a critical need to study anticancer activity of PP, a global food crop, against colon CSCs. Thus, isolated colon CSCs (positive for CD44, CD133 and ALDH1b1 markers) with functioning p53 and shRNA-attenuated p53 were treated with PA at 5.0 μg/ml. Effects of baked PP (20% wt/wt) against colon CSCs were also tested in vivo in mice with azoxymethane-induced colon tumorigenesis. Effects of PA/PP were compared to positive control sulindac. In vitro, PA suppressed proliferation and elevated apoptosis in a p53-independent manner in colon CSCs. PA, but not sulindac, suppressed levels of Wnt pathway effector β-catenin (a critical regulator of CSC proliferation) and its downstream proteins (c-Myc and cyclin D1) and elevated Bax and cytochrome c, proteins-mediating mitochondrial apoptosis. In vivo, PP reduced the number of crypts containing cells with nuclear β-catenin (an indicator of colon CSCs) via induction of apoptosis and suppressed tumor incidence similar to that of sulindac. Combined, our data suggest that PP may contribute to reduced colon CSCs number and tumor incidence in vivo via suppression of Wnt/β-catenin signaling and elevation of mitochondria-mediated apoptosis.