Journal
JOURNAL OF ETHNOPHARMACOLOGY
Volume 142, Issue 2, Pages 523-530Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2012.05.030
Keywords
Ethnobotanicals; Akt inhibition; Caspase-3 activation; TUNEL assay; Xenograft; BxPC-3-luc-2
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Funding
- American Cancer Society
- Dr. John T. Macdonald Foundation
- Paul and Mary Sheibar Foundation
- NIH [1R01AT003544, R01CA156776-01]
- University of Miami
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Ethnopharmacological relevance: Achyranthes aspera (Family Amaranthacea) is used for cancer therapy by ayurvedic medical practitioners in India. However, due to the non formal nature of its use, there are no systematic studies validating its medicinal properties. Thus, it's utility as an anti cancer agent remains anecdotal. Earlier, we demonstrated A. aspera to exhibit time and dose-dependent preferential cytotoxicity to cultured human pancreatic cancer cells. In this report we validate in vivo anti tumor properties of A. aspera. Materials and methods: The in vivo anti tumor activity of leaf extract (LE) was tested by intraperitoneal (IP) injections into athymic mice harboring human pancreatic tumor subcutaneous xenograft. Toxicity was monitored by recording changes in behavioral, histological, hematological and body weight parameters. Results: Dosing LE to athymic mice by I.P. injection for 32 days showed no adverse reactions in treated mice. Compared to the control set, IP administration of LE to tumor bearing mice significantly reduced both tumor weight and volume. Gene expression analysis using Real time PCR methods revealed that LE significantly induced caspase-3 mRNA (p < 0.001) and suppressed expression of the pro survival kinase Akt-1 (p < 0.05). TUNEL assay and immunohistochemistry confirmed apoptosis induction by activation of caspase-3 and inhibiting Akt phosphorylation in treated sets. These results are in agreement with RT PCR data. Conclusion: Taken together, these data suggest A. aspera to have potent anti cancer property. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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