Related Experiment Video
Updated: Jan 20, 2026
Chemical-induced Two-stage Skin Carcinogenesis Model: An Experimental In Vivo Mouse Model of Skin Cancer
Published on: April 30, 2023
Modulation of cancer signalling pathway(s) in two -stage mouse skin tumorigenesis by annonacin
Mohd Rohaizad Md Roduan1, Roslida Abd Hamid2, Norhafizah Mohtarrudin3
1Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
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.
Insights
Annonacin, a compound from Annona muricata, effectively inhibited skin tumor promotion in mice by modulating key cancer signaling pathways. This study demonstrates its potential as a therapeutic agent with no observed liver or kidney toxicity.
Area of Science:
- Pharmacology
- Oncology
- Natural Products Chemistry
Background:
- Annonacin, an acetogenin from Annona muricata, exhibits in vitro cytotoxicity.
- Its in vivo antitumor-promoting activity remains largely uninvestigated.
Purpose of the Study:
- To evaluate the antitumor-promoting effects of annonacin using a two-stage mouse skin tumorigenesis model.
- To elucidate the molecular mechanisms underlying annonacin's activity.
Main Methods:
- Mice were induced with 7,12-dimethylbenz[α]anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA).
- Annonacin was applied topically before TPA treatment for 22 weeks.
- Histopathological and molecular analyses (gene and protein expression) were performed.
Main Results:
- Annonacin significantly delayed tumor onset and reduced tumor incidence, burden, and volume.
- It suppressed skin hyperkeratosis and keratin pearl formation.
- Modulation of AKT, ERK, mTOR, p38, PTEN, and Src signaling pathways was observed.
- Annonacin showed no apparent toxicity to the liver or kidneys.
Conclusions:
- Annonacin demonstrates significant antitumor-promoting activity in a mouse skin cancer model.
- It targets multiple cancer signaling pathways involved in tumor promotion.
- Annonacin is a potential therapeutic candidate for skin tumorigenesis with a favorable safety profile.
More Related Videos
07:46In vivo Imaging and Therapeutic Treatments in an Orthotopic Mouse Model of Ovarian Cancer
Published on: August 17, 2010
06:46Mouse Fetal Whole Intestine Culture System for Ex Vivo Manipulation of Signaling Pathways and Three-dimensional Live Imaging of Villus Development
Published on: September 4, 2014
Related Concept Videos
03:02Chemical-induced Two-stage Skin Carcinogenesis Model: An Experimental In Vivo Mouse Model of Skin Cancer
07:46In vivo Imaging and Therapeutic Treatments in an Orthotopic Mouse Model of Ovarian Cancer
06:46Mouse Fetal Whole Intestine Culture System for Ex Vivo Manipulation of Signaling Pathways and Three-dimensional Live Imaging of Villus Development
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
03:14Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
02:33Hedgehog Signaling Pathway