Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Jean Christopher Chamcheu
* ORCID logo ,
Islam Rady
,
Roxane-Cherille N. Chamcheu
,
Abu Bakar Siddique
ORCID logo ,
Melissa B. Bloch
ORCID logo ,
Sergette Banang Mbeumi
,
Abiola S. Babatunde
,
Mohammad B. Uddin
,
Felicite K. Noubissi
ORCID logo ,
Peter W. Jurutka
ORCID logo ,
Yong-Yu Liu
,
Vladimir S. Spiegelman
,
G. Kerr Whitfield
,
Khalid A. El Sayed
ORCID logo
Version 1 : Received: 1 June 2018 / Approved: 1 June 2018 / Online: 1 June 2018 (13:00:02 CEST)

A peer-reviewed article of this Preprint also exists.

Chamcheu, 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. 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. Int. J. Mol. Sci. 2018, 19, 1791. Chamcheu, 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. 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. Int. J. Mol. Sci. 2018, 19, 1791.

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; ii) induce G0/G1 cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iv) 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

Keywords

Annona muricata; apoptosis; basal cell carcinoma; cutaneous squamous cell carcinoma; graviola; Hedgehog signaling pathway; natural products chemistry; non-melanoma skin cancer

Subject

Medicine and Pharmacology, Dermatology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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