Poly[3-(3, 4-dihydroxyphenyl) glyceric acid] from Comfrey exerts anti-cancer efficacy against human prostate cancer via targeting androgen receptor, cell cycle arrest and apoptosis
Open Access
- 12 June 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 33 (8), 1572-1580
- https://doi.org/10.1093/carcin/bgs202
Abstract
The major obstacles in human prostate cancer (PCA) treatment are the development of resistance to androgen ablation therapy leading to hormone-refractory state and the toxicity associated with chemotherapeutic drugs. Thus, the identification of additional non-toxic agents that are effective against both androgen-dependent and androgen-independent PCA is needed. In the present study, we investigated the efficacy of a novel phytochemical poly[3-(3, 4-dihydroxyphenyl)glyceric acid] (p-DGA) from Caucasian species of comfrey (Symphytum caucasicum) and its synthetic derivative syn-2, 3-dihydroxy-3-(3, 4-dihydroxyphenyl) propionic acid (m-DGA) against PCA LNCaP and 22Rv1 cells. We found that both p-DGA and m-DGA suppressed the growth and induced death in PCA cells, with comparatively lesser cytotoxicity towards non-neoplastic human prostate epithelial cells. Furthermore, we also found that both p-DGA and m-DGA caused G1 arrest in PCA cells through modulating the expression of cell cycle regulators, especially an increase in CDKIs (p21 and p27). In addition, p-DGA and m-DGA induced apoptotic death by activating caspases, and also strongly decreased AR and PSA expression. Consistent with in vitro results, our in vivo study showed that p-DGA feeding strongly inhibited 22Rv1 tumors growth by 76% and 88% at 2.5 and 5mg/kg body weight doses, respectively, without any toxicity, together with a strong decrease in PSA level in plasma; and a decrease in PCNA, AR and PSA expression but increase in p21/p27 expression and apoptosis in tumor tissues from p-DGA-fed mice. Overall, present study identifies p-DGA as a potent agent against PCA without any toxicity, and supports its clinical application.Keywords
This publication has 41 references indexed in Scilit:
- Antimetastatic efficacy of silibinin: molecular mechanisms and therapeutic potential against cancerCancer and Metastasis Reviews, 2010
- Gallic Acid, an Active Constituent of Grape Seed Extract, Exhibits Anti-proliferative, Pro-apoptotic and Anti-tumorigenic Effects Against Prostate Carcinoma Xenograft Growth in Nude MicePharmaceutical Research, 2009
- Grape Seed Extract Induces Cell Cycle Arrest and Apoptosis in Human Colon Carcinoma CellsNutrition and Cancer, 2008
- Natural products in drug discoveryDrug Discovery Today, 2008
- Cancer as an overhealing wound: an old hypothesis revisitedNature Reviews Molecular Cell Biology, 2008
- AR, the cell cycle, and prostate cancerNuclear Receptor Signaling, 2008
- A promoting role of androgen receptor in androgen-sensitive and -insensitive prostate cancer cellsNucleic Acids Research, 2007
- A cancer chemopreventive agent silibinin, targets mitogenic and survival signaling in prostate cancerMutation research. Reviews in mutation research, 2004
- Molecular determinants of resistance to antiandrogen therapyNature Medicine, 2003
- The Hallmarks of CancerCell, 2000