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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2019

Open Access 01-12-2019 | Research article

Modulation of cancer signalling pathway(s) in two -stage mouse skin tumorigenesis by annonacin

Authors: Mohd Rohaizad Md Roduan, Roslida Abd Hamid, Norhafizah Mohtarrudin

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

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Abstract

Background

Annonacin, an annonaceous acetogenin isolated from Annona muricata has been reported to be strongly cytotoxic against various cell lines, in vitro. Nevertheless, its effect against in vivo tumor promoting activity has not been reported yet. Therefore, this study was aimed to investigate antitumor-promoting activity of annonacin via in vivo two-stage mouse skin tumorigenesis model and its molecular pathways involved.

Methods

Mice were initiated with single dose of 7,12-dimethylbenz[α]anthracene (DMBA) (390 nmol/100 μL) followed by, in subsequent week, repeated promotion (twice weekly; 22 weeks) with 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 μL). Annonacin (85 nM) and curcumin (10 mg/kg; reference) were, respectively, applied topically to DMBA/TPA-induced mice 30 min before each TPA application for 22 weeks. Upon termination, histopathological examination of skin, liver and kidney as well as genes and proteins expression analysis were conducted to elucidate the potential mechanism of annonacin.

Results

With comparison to the carcinogen control, Annonacin significantly increased the tumor latency period and reduced the tumor incidence, tumor burden and tumor volume, respectively. In addition, it also suppressed tumorigenesis manifested by significant reduction of hyperkeratosis, dermal papillae and number of keratin pearls on skin tissues. Annonacin also appeared to be non-toxic to liver and kidney. Significant modulation of both AKT, ERK, mTOR, p38, PTEN and Src genes and proteins were also observed in annonacin-targeted signaling pathway(s) against tumorigenesis.

Conclusions

Collectively, results of this study indicate that annonacin is a potential therapeutic compound targeting tumor promoting stage in skin tumorigenesis by modulating multiple gene and protein in cancer signaling pathways without apparent toxicity.
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Metadata
Title
Modulation of cancer signalling pathway(s) in two -stage mouse skin tumorigenesis by annonacin
Authors
Mohd Rohaizad Md Roduan
Roslida Abd Hamid
Norhafizah Mohtarrudin
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-019-2650-1

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