Polar biophenolics in sweet potato greens extract synergize to inhibit prostate cancer cell proliferation and in vivo tumor growth

• Published in: Carcinogenesis (New York) Vol. 34; no. 9; pp. 2039 - 2049
• Main Authors: Gundala, Sushma R, Yang, Chunhua, Lakshminarayana, N, Asif, Ghazia, Gupta, Meenakshi V, Shamsi, Shahab, Aneja, Ritu
• Format: Journal Article
• Language: English
• Published: England 01.09.2013
• Subjects: Animals; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Chromatography, High Pressure Liquid; Dietary Supplements; Drug Synergism; Humans; Ipomoea batatas - chemistry; Male; Mice; Plant Extracts - administration & dosage; Plant Extracts - chemistry; Polyphenols - administration & dosage; Polyphenols - chemistry; Prostatic Neoplasms - diet therapy; Prostatic Neoplasms - pathology; Xenograft Model Antitumor Assays
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgt141

Polyphenolic phytochemicals present in fruits and vegetables indisputably confer anticancer benefits upon regular consumption. Recently, we demonstrated the growth-inhibitory and apoptosis-inducing properties of polyphenol-rich sweet potato greens extract (SPGE) in cell culture and in vivo prostate cancer xenograft models. However, the bioactive constituents remain elusive. Here, we report a bioactivity-guided fractionation of SPGE based upon differential solvent polarity using chromatographic techniques that led to the identification of a remarkably active polyphenol-enriched fraction, F5, which was ~100-fold more potent than the parent extract as shown by IC50 measurements in human prostate cancer cells. High-performance liquid chromatography-ultraviolet and mass spectrometric analyses of the seven SPGE fractions suggested varying abundance of the major phenols, quinic acid (QA), caffeic acid, its ester chlorogenic acid, and isochlorogenic acids, 4,5-di-CQA, 3,5-di-CQA and 3,4-di-CQA, with a distinct composition of the most active fraction, F5. Subfractionation of F5 resulted in loss of bioactivity, suggesting synergistic interactions among the constituent phytochemicals. Quantitative analyses revealed a ~2.6- and ~3.6-fold enrichment of QA and chlorogenic acid, respectively, in F5 and a definitive ratiometric relationship between the isochlorogenic acids. Daily oral administration of 400mg/kg body wt of F5 inhibited growth and progression of prostate tumor xenografts by ~75% in nude mice, as evidenced by tumor volume measurements and non-invasive real-time bioluminescence imaging. These data generate compelling grounds to further examine the chemopreventive efficacy of the most active fraction of SPGE and suggest its potential usefulness as a dietary supplement for prostate cancer management.