Article Publish Status: FREE
Abstract Title:

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.

Abstract Source:

Int J Mol Sci. 2018 Jun 16 ;19(6). Epub 2018 Jun 16. PMID: 29914183

Abstract Author(s):

Jean Christopher Chamcheu, Islam Rady, Roxane-Cherille N Chamcheu, Abu Bakar Siddique, Melissa B Bloch, Sergette Banang Mbeumi, Abiola S Babatunde, Mohammad B Uddin, Felicite K Noubissi, Peter W Jurutka, Yong-Yu Liu, Vladimir S Spiegelman, G Kerr Whitfield, Khalid A El Sayed

Article Affiliation:

Jean Christopher Chamcheu


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 (), 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 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 theirconstituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs.

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