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Graviola (Annona muricata) Exerts Anti-Proliferative, Anti-Clonogenic and Pro-Apoptotic Effects in Human Non-Melanoma Skin Cancer UW-BCC1 and A431 Cells In Vitro: Involvement of Hedgehog Signaling
- Source :
- International Journal of Molecular Sciences, Vol 19, Iss 6, p 1791 (2018), International Journal of Molecular Sciences, Volume 19, Issue 6
- Publication Year :
- 2018
- Publisher :
- MDPI AG, 2018.
-
Abstract
- Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: (i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity<br />(ii) induce G0/G1 cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iii) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs.
- Subjects :
- 0301 basic medicine
Hedgehog signaling pathway
Skin Neoplasms
Cell cycle checkpoint
Annona muricata
cutaneous squamous cell carcinoma
Annona
lcsh:Chemistry
0302 clinical medicine
Cell Movement
lcsh:QH301-705.5
Tumor Stem Cell Assay
Spectroscopy
biology
Cell Cycle
apoptosis
General Medicine
Cell cycle
3. Good health
Computer Science Applications
dermatology
030220 oncology & carcinogenesis
A431 cells
non-melanoma skin cancer
Signal Transduction
natural products chemistry
graviola
Antineoplastic Agents
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
basal cell carcinoma
Cyclin-dependent kinase
Cell Line, Tumor
Humans
Hedgehog Proteins
Physical and Theoretical Chemistry
Molecular Biology
Cell Proliferation
Plant Extracts
Cell growth
Organic Chemistry
biology.organism_classification
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Apoptosis
biology.protein
Cancer research
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 19
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....c64f2b256bb68204ad4ca1b8e4880044