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

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dc.contributor.authorChamcheu, Jean Chris
dc.contributor.authorRady, Islam
dc.contributor.authorChamcheu, Roxane-Cherille
dc.contributor.authorSiddique, Abu Bakar
dc.contributor.authorBloch, Melissa
dc.contributor.authorMbeumi, Sergette Banang
dc.contributor.authorBabatunde, Abiola S.
dc.contributor.authorUddin, Mohammad B.
dc.contributor.authorNoubissi, Felicite K.
dc.contributor.authorJurutka, Peter W.
dc.contributor.authorLiu, Yong-Yu
dc.contributor.authorSpiegelman, Vladimir S.
dc.contributor.authorWhitfield, G. Kerr
dc.contributor.authorEl Sayed, Khalid A.
dc.date.accessioned2020-05-23T00:16:28Z
dc.date.available2020-05-23T00:16:28Z
dc.date.issued2018
dc.description.abstractAbstract: 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; (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.en_US
dc.identifier.citationChamcheu, J.C.; Rady, I.; Chamcheu, R.-C.N.; Siddique, A.B.; Bloch, M.B.; Banang Mbeumi, S.; Babatunde, A.S.; Uddin, M.B.; Noubissi, F.K.; Jurutka, P.W.; Liu, Y.-Y.; Spiegelman, V.S.; Whitfield, G.K.; & El Sayed, K.A. (2018) 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, 19:1791 - 1815.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/4009
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.subjectAnnona muricata;en_US
dc.subjectapoptosis;en_US
dc.subjectcutaneous squamous cell carcinomaen_US
dc.subjectbasal cell carcinoma;en_US
dc.titleGraviola (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 Signalingen_US
dc.title.alternativeAnnona muricata; apoptosis; basal cell carcinoma; cutaneous squamous cell carcinomaen_US
dc.typeArticleen_US

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