Home' Australian Pharmacist : Australian Pharmacist Oct 2013 Contents Australian Pharmacist October 2013 I ©Pharmaceutical Society of Australia Ltd. 71
with many yet to be described in the
literature.6 It would seem to follow that
quality control of soursop and its extracts
may be severely compromised by such a
complex array of bioactive compounds,
each of which may present a different
Morton remarked on the presence of the
alkaloids anonaine (syn. annonaine6) and
anoniine.4 Anonaine has a tetracyclic,
isoquinoloid aporphine skeleton and
possesses insecticidal and antimicrobial
properties. 7 Identification of four
alkaloids new to A. muricata , but known
from other plant sources, as asimilobin,
isoboldine, remerine and liriodenine,
supplemented earlier studies by these
authors8 which had identified anonaine,
xylopine, isolaureline and coclaurine, as
well as N-methylcoclaurine in this study.9
These alkaloids, or at least some of them,
seem to be connected with the production
of movement disorders and are toxic to
dopaminergic and GABA-nergic neurons in
low concentrations.10 This would appear to
link them with the action of the previously
mentioned acetogenin, annonacin, (and
probably other related compounds as well).
The constituent story is very complex with
new compounds being announced on a
regular basis. Obviously soursop has excited
interest as searches continue for effective
But what of the reported activity? Given
that all parts of the tree have been used
in traditional medicine as 'antihelmintic,
antiplasmodial, antiparasitic, antimicrobial,
antipyretic, sedative, antispasmodic,
nervine, hypotenmsive, anticonvulsant,
digestive, antitumour and anticancer'
agents,11 the potential for investigation
would appear to be quite exhaustive!
Nevertheless, certain specific actions have
been further characterised. For instance,
while antiplasmodial action against the
malarial Plasmodium falciparum strain W2
has been demonstrated in Cameroonian A.
muricata leaves, twigs and fruit methanolic
extracts, concerns were expressed about
the toxicity profile of the extracts.12
Returning to the question of anticancer
activity in A. muricata, and with pertinent
criticism by 'Hoax-Slayer', a firm statement
is made that 'The author of the message
has taken a core of truthful information
from scientific studies pertaining to graviola
and extrapolated wildly, tacking on a host
of false assumptions, misused statistics
and ridiculous accusations in a rather lame
attempt to make her claims sound more
credible'.2 Strong words, but reasonably
reflecting comment which can be made
about a number of such online claims of
The critique goes on to affirm that, yes,
anticancer activity has been demonstrated
in some types of liver and breast cancer
cells that are resistant to particular
chemotherapeutic drugs, but not yet in
large scale human trials. It would also
appear that 'reputable scientific cancer
organisations' do not support internet
advertisements about graviola as a cancer
cure, nor is there 'evidence of safety
However, and accepting Christensens's
criticism as reasonable, ongoing research
continues to demonstrate anticancer
activity. For example, in vitro and in vivo
evaluation of the action of a graviola
extract on pancreatic cancer cells showed
necrosis of the cells by inhibition of their
metabolism.13 Many of the multiple
signalling pathways involving molecules
such as HIF-1a, NF-kB, GLUT1, GLUT4,
HKII and LDHA regulating metabolism,
cell cycle, survival and metastasis were
down regulated.13 The in vivo studies
were performed on 6--8 week old female
athymic immunodeficient mice following
placement of luciferase-expressing CD18/
HPAF cells into the pancreas, whence
significant decrease in tumour growth was
observed, as well as tumour necrosis and
reduced metastasis. These results are very
exciting given that pancreatic tumours
are often aggressive and resistant to
Graviola fruit extract has also been
demonstrated to significantly
down-regulate epidermal growth factor
receptor, which is often over-expressed in
breast cancer. Treatment of tumorigenic
breast cancer cell lines arrested cell cycling
and induced apoptosis, and inhibited
tumour growth in a mouse xenograft model
following dietary administration of
This article has dealt solely with A. muricata,
but other species such as A. montana
and A. squamosa do occur. They also are
rich in acetogenins, and have proved
active against selected human cell lines,
however further discussion is limited here by
Finally, and writing with my medicinal
chemical hat on, it has been exciting to note
that synthetic analogues of the acetogenins,
(-)- and (+)- muricatacin, synthesised from
monsaccharide precursors, are active against
human oesophageal carcinoma cell lines15
and other human malignant cell lines.16
A black cloud yet to be cleared from the
horizon of the use of Graviola extracts and
constituents is the question of toxicity.
In addition to the neurochemical toxicity
previously mentioned, the discovery
of iminosugars, such as the neurotoxic
swainsonine, suggests the need for caution
in the use of Graviola.17 Nevertheless,
anticancer activity has definitely been
demonstrated, and this at least opens the
door to extensive further investigation in
attempts to refine the specificity of action.
1. Oxalis pes-caprae. Wikipedia, the free encyclopedia; available at
http://en.wikipedia.org/wiki/Oxalis_pes-caprae, and references
2. Christensen B. Is sour sop a cancer killer 10,000 times stronger than
chemotherapy? Mar 2013; available at http://www.hoax-slayer.
3. Soursop Fruit Kills Cancer 100-Fold better Than Chemotherapy;
available at http://www.sott.net/article/242555-Soursop-Fruit-Kills-
4. Morton, J. Soursop. Fruits of warm climates. 1987.
Julia F. Morton ,Miami, FL. 33189; available at http://www.hort.
5. Bruneton J. Pharmacognosy, Phytochemistry, Medicinal Plants.
Andover UK 1995. Intercept Limited [Lavoisier Publishing
6. Le Ven J, Schmitz-Afonso I, Lewin G et al., Comprehensive
characterization of Annonaceous acetogenins within a complex
extract by HPLC-ESI-LTQ-Orbitrap using post-column lithium
infusion. J Mass Spectrom. 2012;47:1500-1509.
7. Phytochemical Dictionary - a Handbook of Bioactive Compounds
from Plants. Eds. Harborne JB & Baxter H. London1993. Taylor &
Francis Ltd;194 (PD 688).
8. Fofana S, Ziyaev R, Abdusamatov A, Zakirov SKh. Alkaloids from
Annona muricata leaves. Chem Nat Comp. May 2011;47(2):321.
9. Fofana S, Keita A, Balde S et al., Alkaloids from leaves of Annona
muricata. Chem Nat Comp. Sep 2012;48(4):714.
10. Annona muricata. Division of Graduate Medical Sciences, Boston
University School of Medicine, Boston Healing Landscape Project;;
available at http://www.bu.edu/bhlp/Clinical/cross-cultural/
11. Pinto AC, Andrade SR, Ferreira FR, Kinpara DI. Annona Species.
International center for Underutilised Crops, University of
Southampton, Southampton SO17 1BJ, UK (2005) pp 1-281.
12. Boyom FF, Fokou PVT, Yamthe LRT et al., Potent antiplasmodial
extracts from Cameroonian Annonaceae. J Ethnopharm. Apr
13. 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 vivo through altering cell
metabolism. Cancer Letters. Oct 2012;323(1):29-40.
14. Dai YM, Hogan S, Schmetz 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. Jul
15. Tsai YF, Huang CC, Lin SH et al., Asymmetric synthesis of
(-)-muricatacin's analogue (4S,5R-5-hydroxy-4-octadecanolide
exhibiting the cytotoxicity against esophageal cancer cell.
Heterocyc. Feb 2012;85(2):299-304.
16. Sreco B, Benedekovic G, Popsavin M et al., Heteroannelated
(+)-muricatacin mimics: synthesis, antiproliferative properties and
structure-activity relationships. Dec 2011;67(48):9358-9367.
17. Mohanty S, Hollinshead J, Jones I, et al., Annona muricata
(Graviola): Toxic or therapeutic. Nat Prod Commun. 2008;3(1):31-33.
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