Document Detail


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.
MedLine Citation:
PMID:  22693258     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 G(1) 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.
Authors:
Sangeeta Shrotriya; Deep Gagan; Kumaraguruparan Ramasamy; Komal Raina; Vakhtang Barbakadze; Maia Merlani; Lali Gogilashvili; Lela Amiranashvili; Karen Mulkijanyan; Kyriakos Papadopoulos; Chapla Agarwal; Rajesh Agarwal
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-12
Journal Detail:
Title:  Carcinogenesis     Volume:  33     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-14     Completed Date:  2012-11-05     Revised Date:  2014-01-06    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  1572-80     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Blotting, Western
Cell Cycle / drug effects*
Comfrey / chemistry*
Enzyme-Linked Immunosorbent Assay
Glyceric Acids / pharmacology*
Humans
Male
Plant Extracts / pharmacology*
Prostatic Neoplasms / pathology,  prevention & control*
Xenograft Model Antitumor Assays
Grant Support
ID/Acronym/Agency:
P30 CA046934/CA/NCI NIH HHS; P30 CA046934/CA/NCI NIH HHS; R01 CA102514/CA/NCI NIH HHS; R01 CA102514/CA/NCI NIH HHS; R01 CA91883/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Glyceric Acids; 0/Plant Extracts; 0/poly(3-(3,4-dihydroxyphenyl)glyceric acid)
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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