Achyranthes aspera (Apamarg) leaf extract inhibits human pancreatic tumor growth in athymic mice by apoptosis

Pochi R. Subbarayan, Malancha Sarkar, Shamaladevi Nagaraja Rao, Sakhi Philip, Pradeep Kumar, Norman Altman, Isildinha Reis, Mansoor Ahmed, Bach Ardalan, Balakrishna L Lokeshwar

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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, its 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.

Original languageEnglish (US)
Pages (from-to)523-530
Number of pages8
JournalJournal of Ethnopharmacology
Volume142
Issue number2
DOIs
StatePublished - Jul 13 2012
Externally publishedYes

Fingerprint

Achyranthes
Nude Mice
Apoptosis
Growth
Neoplasms
Tumor Burden
Caspase 3
Amaranthaceae
In Situ Nick-End Labeling
Intraperitoneal Injections
Pancreatic Neoplasms
Heterografts
Real-Time Polymerase Chain Reaction
India
Phosphotransferases
Immunohistochemistry
Body Weight
Phosphorylation
Gene Expression
Polymerase Chain Reaction

Keywords

  • Akt inhibition
  • BxPC-3-luc-2
  • Caspase-3 activation
  • Ethnobotanicals
  • TUNEL assay
  • Xenograft

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Achyranthes aspera (Apamarg) leaf extract inhibits human pancreatic tumor growth in athymic mice by apoptosis. / Subbarayan, Pochi R.; Sarkar, Malancha; Nagaraja Rao, Shamaladevi; Philip, Sakhi; Kumar, Pradeep; Altman, Norman; Reis, Isildinha; Ahmed, Mansoor; Ardalan, Bach; Lokeshwar, Balakrishna L.

In: Journal of Ethnopharmacology, Vol. 142, No. 2, 13.07.2012, p. 523-530.

Research output: Contribution to journalArticle

Subbarayan, PR, Sarkar, M, Nagaraja Rao, S, Philip, S, Kumar, P, Altman, N, Reis, I, Ahmed, M, Ardalan, B & Lokeshwar, BL 2012, 'Achyranthes aspera (Apamarg) leaf extract inhibits human pancreatic tumor growth in athymic mice by apoptosis', Journal of Ethnopharmacology, vol. 142, no. 2, pp. 523-530. https://doi.org/10.1016/j.jep.2012.05.030
Subbarayan, Pochi R. ; Sarkar, Malancha ; Nagaraja Rao, Shamaladevi ; Philip, Sakhi ; Kumar, Pradeep ; Altman, Norman ; Reis, Isildinha ; Ahmed, Mansoor ; Ardalan, Bach ; Lokeshwar, Balakrishna L. / Achyranthes aspera (Apamarg) leaf extract inhibits human pancreatic tumor growth in athymic mice by apoptosis. In: Journal of Ethnopharmacology. 2012 ; Vol. 142, No. 2. pp. 523-530.
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abstract = "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, its 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.",
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AU - Philip, Sakhi

AU - Kumar, Pradeep

AU - Altman, Norman

AU - Reis, Isildinha

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AU - Ardalan, Bach

AU - Lokeshwar, Balakrishna L

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