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

Abstract

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.

Chlorogenic acid inhibits hypoxia-induced angiogenesis via down-regulation of the HIF-1α/AKT pathway

“…CGA has been used as a chemoprotective agent for chemotherapy in cancer patients by reducing the cytotoxic effects of anticancer drugs through scavenging reactive oxygen species (ROS) [20]. Also, a direct anti-tumor effect of CGA has been noted in various human cancer cells such as prostate cancer cells [21], acute and chronic myeloid leukemia cells [22,23], lung cancer cells [24], colon cancer cells and liver cancer cells [25]. Furthermore, CGA has been found to decrease urethane-induced lung cancer [26], the growth and progression of prostate cancer xenografts [21] and 12-Otetradecanoylphorbol-13-acetate (TPA) induced epithelial cancer in vivo [27].…”

Long Term Effect of Curcumin in Restoration of Tumour Suppressor p53 and Phase-II Antioxidant Enzymes via Activation of Nrf2 Signalling and Modulation of Inflammation in Prevention of Cancer

“…It is not clear whether anti-carcinogenic action of curcumin is due to cumulative effect of its metabolites or due to curcumin itself. Further, it is evidenced that the consumption of whole or partially purified food extracts is more beneficial over single-isolated constituent due to the existence of synergistic interactions among phytochemicals in whole foods [ 20 , 21 ]. Earlier we have reported that anticarcinogenic action of curcumin during its long term effect is mediated via regulation of glycolytic pathway and angiogenesis, as a result of the consequence of modulation of stress activated genes [ 20 ].…”

Antiproliferative and Apoptosis Inducing Effects of Non-Polar Fractions from Lawsonia inermis L. in Cervical (HeLa) Cancer Cells

“…Colonogenic potential of both the fractions was assessed using protocol of Gundala et al (2013) with slight modifications.…”