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
Banang Mbeumi, Sergette
El Sayed, Khalid
AffiliationUniv Arizona, Coll Med Phoenix, Dept Basic Med Sci
basal cell carcinoma
cutaneous squamous cell carcinoma
Hedgehog signaling pathway
natural products chemistry
non-melanoma skin cancer
MetadataShow full item record
CitationChamcheu JC, Rady I, Chamcheu R-CN, Siddique AB, Bloch MB, Banang Mbeumi S, Babatunde AS, Uddin MB, Noubissi FK, Jurutka PW, Liu Y-Y, Spiegelman VS, Whitfield GK, El Sayed KA. 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. International Journal of Molecular Sciences. 2018; 19(6):1791.
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AbstractNon-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; (ii) induce G(0)/G(1) 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.
NoteOpen Access Journal.
VersionFinal published version
SponsorsUniversity of Louisiana at Monroe (ULM), School of Pharmacy; ULM College of Pharmacy Faculty Research Seed Grant [5CALHN-260615]; American Skin Association (ASA); UW-Madison Skin Disease Research Center (SDRC) Pilot and Feasibility Research Award from NIH/NIAMS [P30 AR066524]; POHOFI Inc. Pre-College Intern Scholarship Award; NIH [NIH R15CA16747, R01CA140285]; University of Arizona, Department of Basic Medical Sciences