The use of dietary supplements by patients with cancer has increased significantly over the past 25 years despite insufficient evidence of safety and effectiveness. Finding reliable sources of information about dietary supplements can be daunting. Patients typically rely on family, friends, and the Internet, often receiving misleading information.
The ASCO Post’s Integrative Oncology series is intended to facilitate the availability of evidence-based information on integrative and complementary therapies commonly used by patients with cancer. We chose graviola for this issue because of the growing interest of cancer patients in the herb’s anticancer potential.
Compiled by Barrie R. Cassileth, MS, PhD, and Jyothirmai Gubili, MS, Memorial Sloan Kettering Cancer Center. The free About Herbs website is managed by K. Simon Yeung, PharmD, MBA, LAc, Memorial Sloan Kettering Cancer Center.
Graviola
Scientific name: Annona muricata
Common names: Guanabana, soursop, custard apple, Brazilian pawpaw
Overview
A small, evergreen tree that belongs to the custard apple family, graviola is a native of the tropical areas in Central and South Americas and the Caribbean. Graviola produces heart-shaped edible fruits, the pulp of which is used to make drinks and sherbets.
Graviola also has a long history of medicinal use for treating inflammatory conditions, diabetes, hypertension, insomnia, parasitic infections, and cancer. All parts of the tree including the bark, leaves, fruits, and roots are used in herbal medicine.
Interest in graviola as a potential anticancer agent surged following the discovery of its cytotoxic property in a 1976 plant-screening program by the National Cancer Institute. Annonaceous acetogenins, extracted from different parts of the tree, were found to have cytotoxic effects. These observations have yet to be confirmed in clinical trials. Nevertheless, despite lack of substantial evidence, graviola is heavily promoted as a cancer-fighting herb.
Products containing graviola are available in health food stores and via the Internet in the form of capsules, liquid extracts, juice blend, teas, and tinctures.
The Science
Graviola exerts antiviral,1 antiparasitic,2 cytotoxic,3 anti-inflammatory,4 antiplatelet,5 antidiabetic,6 antihyperglycemic,7 and anticancer effects8,9 in vitro and in vivo.
Mechanistic studies revealed the effectiveness of graviola extracts against the growth of doxorubicin-resistant human mammary adenocarcinoma (MCF-7/Adr) cells by blocking access of cancer cells to adenosine triphosphate and by inhibiting the actions of plasma membrane glycoprotein.10 They also inhibited the expression of hypoxia-inducible factor 1-alpha, nuclear factor kappaB, glucose transporters, and glycolytic enzymes, resulting in decreased glucose uptake and adenosine triphosphate production in pancreatic cancer cells11 as well as downregulated epidermal growth factor receptor expression in breast cancer cells.8
In a rodent model of hepatic cancer, bullatacin, an acetogenin derived from graviola, caused hepato- and nephrotoxicity by increasing calcium concentration, reactive oxygen species production, and expression of the apoptosis regulator Bax and the Bax/Bcl-2 ratio.12
Phenolic compounds of graviola also demonstrated free-radical scavenging potential against human breast carcinoma cells.13 However, human data are lacking.
Of concern are findings that alkaloids extracted from graviola can cause neuronal dysfunction and degeneration.14,15 Graviola also may decrease the uptake of radiopharmaceuticals used in nuclear imaging.16
Adverse Reactions
Repeated consumption of graviola resulted in movement disorders and myeloneuropathy with symptoms mimicking Parkinson’s disease.14,15
Herb-Drug Interactions
Antidiabetics and antihypertensives: Graviola may have additive effects.7,17 ■
Disclosure: Ms. Gubili reported no potential conflicts of interest.
References
1. Padma P, Pramod NP, Thyagarajan SP, et al: Effect of the extract of Annona muricata and Petunia nyctaginiflora on Herpes simplex virus. J Ethnopharmacol 61:81-83, 1998.
2. dos Santos AF, Sant’Ana AE: Molluscicidal properties of some species of Annona. Phytomedicine 8:115-120, 2001.
3. Liaw CC, Chang FR, Lin CY, et al: New cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata. J Nat Prod 5:470-475, 2002.
4. de Sousa OV, Vieira GD, de Jesus RGdPJ, et al: Antinociceptive and anti-inflammatory activities of the ethanol extract of Annona muricata L. leaves in animal models. Int J Mol Sci 11:2067-2078, 2010.
5. Awodele O, Ishola IO, Ikumawoyi VO, et al: Toxicological evaluation of the lyophilized fruit juice extract of Annona muricata Linn. (Annonaceae) in rodents. J Basic Clin Physiol Pharmacol 18:1-11, 2013.
6. Florence NT, Benoit MZ, Jonas K, et al: Antidiabetic and antioxidant effects of Annona muricata (Annonaceae), aqueous extract on streptozotocin-induced diabetic rats. J Ethnopharmacol 151:784-790, 2014.
7. Adeyemi DO, Komolafe OA, Adewole OS, et al: Antihyperglycemic activities of Annona muricata (Linn). Afr J Tradit Complement Altern Med 6:62-69, 2008.
8. Dai Y, Hogan S, Schmelz EM, et al: Selective growth inhibition of human breast cancer cells by graviola fruit extract in vitro and in vivo involving downregulation of EGFR expression. Nutr Cancer 63:795-801, 2011.
9. Hamizah S, Roslida AH, Fezah O, et al: Chemopreventive potential of Annona muricata L leaves on chemically-induced skin papillomagenesis in mice. Asian Pac J Cancer Prev 13:2533-2539, 2012.
10. Oberlies NH, Chang CJ, McLaughlin JL: Structure-activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells. J Med 40:2102-2106, 1997.
11. Torres MP, Rachagani S, Purohit V, et al: Graviola: A novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism. Cancer Lett 323:29-40, 2012.
12. Chen Y, Chen JW, Zhai JH, et al: Antitumor activity and toxicity relationship of annonaceous acetogenins. Food Chem Toxicol 58:394-400, 2013.
13. George VC, Kumar DR, Rajkumar V, et al: Quantitative assessment of the relative antineoplastic potential of the n-butanolic leaf extract of Annona muricata Linn. in normal and immortalized human cell lines. Asian Pac J Cancer Prev 13:699-704, 2012.
14. Lannuzel A, Michel PP, Caparros-Lefebvre D, et al: Toxicity of Annonaceae for dopaminergic neurons: Potential role in atypical parkinsonism in Guadeloupe. Mov Disord 17:84-90, 2002.
15. Lannuzel A, Hoglinger GU, Champy P, et al: Is atypical parkinsonism in the Caribbean caused by the consumption of Annonacae? J Neural Transm Suppl (70):153-157, 2006.
16. Holanda CM, Barbosa DA, Demeda VF, et al: Influence of Annona muricata (soursop) on biodistribution of radiopharmaceuticals in rats. Acta Cir Bras Mar 29:145-150, 2014.
17. Nwokocha CR, Owu DU, Gordon A, et al: Possible mechanisms of action of the hypotensive effect of Annona muricata (soursop) in normotensive Sprague-Dawley rats. Pharm Biol 50:1436-1441, 2012.
GUEST EDITOR
Integrative Oncology is guest edited by Barrie R. Cassileth, MS, PhD, Chief of the Integrative Medicine Service and Laurance S. Rockefeller Chair in Integrative Medicine at Memorial Sloan Kettering Cancer Center, New York.
The Integrative Medicine Service at Memorial Sloan Kettering Cancer Center developed and maintains a free website—About Herbs (www.mskcc.org/aboutherbs)—that provides objective and unbiased information about herbs, vitamins, minerals, and other dietary supplements, and unproved anticancer treatments. Each of the close to 300 and growing number of entries offers health-care professional and patient versions, and entries are regularly updated with the latest research findings.
In addition, the About Herbs app, Memorial Sloan Kettering Cancer Center’s very first mobile application, can be downloaded at http://itunes.apple.com/us/app/about-herbs/id554267162?mt=8. The app is compatible with iPad, iPhone, and iPod Touch devices.
