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Int J Mol Sci. 2018 Jun 16;19(6). pii: E1791. doi: 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.

Author information

1
Department of Basic Pharmaceutical Sciences, School of Pharmacy, College of Health and Pharmaceutic Sciences, University of Louisiana at Monroe, Monroe, 71209-0497 LA, USA. chamcheu@ulm.edu.
2
Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, 53706 WI, USA. chamcheu@ulm.edu.
3
Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, 53706 WI, USA. iabdelaal@wisc.edu.
4
Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, 53706 WI, USA. roxanechamcheu@gmail.com.
5
Madison West High School, 30 Ash St, Madison, 53726 WI, USA. roxanechamcheu@gmail.com.
6
Department of Basic Pharmaceutical Sciences, School of Pharmacy, College of Health and Pharmaceutic Sciences, University of Louisiana at Monroe, Monroe, 71209-0497 LA, USA. siddiqab@warhawks.ulm.edu.
7
Department of Basic Pharmaceutical Sciences, School of Pharmacy, College of Health and Pharmaceutic Sciences, University of Louisiana at Monroe, Monroe, 71209-0497 LA, USA. blochmb@warhawks.ulm.edu.
8
Division for Research and Innovation, POHOFI Inc., P.O. Box 44067, Madison, 53744 WI, USA. sbmbeumi@pohofi.org.
9
Department of Basic Pharmaceutical Sciences, School of Pharmacy, College of Health and Pharmaceutic Sciences, University of Louisiana at Monroe, Monroe, 71209-0497 LA, USA. asbabatunde@unilorin.edu.ng.
10
Department of Basic Pharmaceutical Sciences, School of Pharmacy, College of Health and Pharmaceutic Sciences, University of Louisiana at Monroe, Monroe, 71209-0497 LA, USA. burhan1129@gmail.com.
11
Department of Biology, Jackson State University, Jackson, 39217 MS, USA. felicite.noubissi_kamdem@jsums.edu.
12
School of Mathematical and Natural Sciences, Arizona State University, Phoenix, 85306 AZ, USA. peter.jurutka@asu.edu.
13
Department of Basic Pharmaceutical Sciences, School of Pharmacy, College of Health and Pharmaceutic Sciences, University of Louisiana at Monroe, Monroe, 71209-0497 LA, USA. yliu@ulm.edu.
14
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University, College of Medicine, Hershey, 17033 PA, USA. vspiegelman@pennstatehealth.psu.edu.
15
Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, 85004 AZ, USA. gkw@email.arizona.edu.
16
Department of Basic Pharmaceutical Sciences, School of Pharmacy, College of Health and Pharmaceutic Sciences, University of Louisiana at Monroe, Monroe, 71209-0497 LA, USA. elsayed@ulm.edu.

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.

KEYWORDS:

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

PMID:
29914183
PMCID:
PMC6032424
DOI:
10.3390/ijms19061791
[Indexed for MEDLINE]
Free PMC Article

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