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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.

التفاصيل البيبلوغرافية
العنوان: 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.
المؤلفون: Chamcheu JC; 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.; Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, 53706 WI, USA. chamcheu@ulm.edu., Rady I; Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, 53706 WI, USA. iabdelaal@wisc.edu., Chamcheu RN; Department of Dermatology, School of Medicine and Public Health, University of Wisconsin, Madison, 53706 WI, USA. roxanechamcheu@gmail.com.; Madison West High School, 30 Ash St, Madison, 53726 WI, USA. roxanechamcheu@gmail.com., Siddique AB; 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., Bloch MB; 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., Banang Mbeumi S; Division for Research and Innovation, POHOFI Inc., P.O. Box 44067, Madison, 53744 WI, USA. sbmbeumi@pohofi.org., Babatunde AS; 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., Uddin MB; 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., Noubissi FK; Department of Biology, Jackson State University, Jackson, 39217 MS, USA. felicite.noubissi_kamdem@jsums.edu., Jurutka PW; School of Mathematical and Natural Sciences, Arizona State University, Phoenix, 85306 AZ, USA. peter.jurutka@asu.edu., Liu YY; 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., Spiegelman VS; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University, College of Medicine, Hershey, 17033 PA, USA. vspiegelman@pennstatehealth.psu.edu., Whitfield GK; Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, Phoenix, 85004 AZ, USA. gkw@email.arizona.edu., El Sayed KA; 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.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2018 Jun 16; Vol. 19 (6). Date of Electronic Publication: 2018 Jun 16.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Annona/*chemistry , Antineoplastic Agents/*pharmacology , Apoptosis/*drug effects , Cell Proliferation/*drug effects , Plant Extracts/*pharmacology , Skin Neoplasms/*metabolism, Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Hedgehog Proteins/genetics ; Hedgehog Proteins/metabolism ; Humans ; Signal Transduction ; Tumor Stem Cell Assay
مستخلص: 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.
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معلومات مُعتمدة: R01 AR063361 United States AR NIAMS NIH HHS; R21 CA191550 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Annona muricata; Hedgehog signaling pathway; apoptosis; basal cell carcinoma; cutaneous squamous cell carcinoma; graviola; natural products chemistry; non-melanoma skin cancer
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Hedgehog Proteins)
0 (Plant Extracts)
تواريخ الأحداث: Date Created: 20180620 Date Completed: 20181010 Latest Revision: 20230926
رمز التحديث: 20230926
مُعرف محوري في PubMed: PMC6032424
DOI: 10.3390/ijms19061791
PMID: 29914183
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms19061791