Biopolymers

The water-soluble high-molecular (>1000 kDa) fractions were isolated by ultrafiltration and gel chromatography on a Sepharose 2B column. According to IR, 13C, 1H NMR, 1D NOE, 2D heteronuclear 1H/13C HSQC spectral data and 2D DOSY experiment the main structural element of these preparations was found to be a regularly substituted polyoxyethelene, namely poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene] (POCDPE). Its synthetic monomer 3-(3,4-dihydroxyphenyl)glyceric acid (DPGA) was synthesized via Sharpless asymmetric dihydroxylation (AD) of trans-caffeic acid derivatives. POCDPE is the first representative of a new class of natural regular polyethers with a 3-(3,4-dihydroxyphenyl)glyceric acid residue as the repeating unit. We found that both POCDPE and DPGA suppressed the growth and induced death in PCA cells, with comparatively lesser cytotoxicity towards non-neoplastic human prostate epithelial cells. We also found that both POCDPE and DPGA caused G1 arrest in PCA cells. In addition, POCDPE and DPGA induced apoptotic death by activating caspases, and also strongly decreased androgen receptor (AR) and prostate specific antigen (PSA) expression. However, our results clearly showed that anticancer efficacy of POCDPE is more effective compared to its synthetic monomer. In summary, our studies for the first time revealed that novel phytochemical POCDPE inhibits the growth of PCA cells both in vitro and in vivo. Results also revealed the broad spectrum effects of POCDPE on AR and PSA levels, cell cycle, and apoptosis revealing some of the plausible underlying mechanisms. In conclusion, present study is significant as we identified a natural nontoxic compound with efficacy against PCA that supports its further pre-clinical and clinical testing.