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Int. J. Mol. Sci. 2018, 19(6), 1791; https://doi.org/10.3390/ijms19061791

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

1
Department of Basic Pharmaceutical Sciences, School of Pharmacy, College of Health and Pharmaceutic Sciences, University of Louisiana at Monroe, Monroe, LA 71209-0497, USA
2
Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA
3
Madison West High School, 30 Ash St, Madison, WI 53726, USA
4
Division for Research and Innovation, POHOFI Inc., P.O. Box 44067, Madison, WI 53744, USA
5
Department of Biology, Jackson State University, Jackson, MS 39217, USA
6
School of Mathematical and Natural Sciences, Arizona State University, Phoenix, AZ 85306, USA
7
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University, College of Medicine, Hershey, PA 17033, USA
8
Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, AZ 85004, USA
Current address: West Monroe High School, 201 Riggs Street, West Monroe, LA 71291, USA.
Current address: Department of Hematology, University of Ilorin, P.M.B 1515, Ilorin, 240001 Kwara State, Nigeria.
*
Author to whom correspondence should be addressed.
Received: 3 May 2018 / Revised: 9 June 2018 / Accepted: 12 June 2018 / Published: 16 June 2018
(This article belongs to the Section Bioactives and Nutraceuticals)
Full-Text   |   PDF [3756 KB, uploaded 21 June 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; (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. View Full-Text
Keywords: Annona muricata; apoptosis; basal cell carcinoma; cutaneous squamous cell carcinoma; graviola; Hedgehog signaling pathway; natural products chemistry; non-melanoma skin cancer Annona muricata; apoptosis; basal cell carcinoma; cutaneous squamous cell carcinoma; graviola; Hedgehog signaling pathway; natural products chemistry; non-melanoma skin cancer
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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 (CC BY 4.0).

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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.

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