Annona muricata (The cancer killer): A review

The Global Journal of Pharmaceutical Research Vol. 2(1), pp. 1613-1618, 31 Mar, 2013; www.tgjpr.com 

FULL LENGTH REVIEW ARTICLE ISSN 2277-5439 

Annona muricata (The cancer killer): A review 

Shaily Mishra* 1 , Shamim Ahmad 1 , Nilesh Kumar 1 , Brijesh Kumar Sharma 1 

1 Translam Institute of Pharmaceutical Education and Research, Meerut (U.P) 

Corresponding Address: shailyshukla1177@yahoo.co.in 

During past several years, there has been growing interest among the usage of 

various medicinal plants from traditional system of medicine for the treatment of 

different ailments. Traditional system of medicine consists of large number of 

plants with various medicinal and pharmacological importances and hence 

represents a priceless tank of new bioactive molecules. (Arunjyothi B). An 

attempt has been made to review Annona Muricata used for the prevention and 

treatment of cancer. The phytochemicals present in the plant possess antioxidant 

activities, which prevent or can be used in the treatment of many diseases, 

including cancer. The drug is also known to have good immunomodulatory 

properties. These act by stimulating both non-specific and specific immunity. 

KEYWORDS: Annona Muricata, Medicinal plants, Phytochemicals, Imuunomodulatory. 

INTRODUCTION 

Herbal medicines have been used since 

the dawn of civilization to maintain health 

and to treat various diseases. To compete 

with the growing pharmaceutical market, 

there is an importance to use and 

scientifically authenticate more 

medicinally useful herbal products. 

(Maity,et.al., 2011) 

Annona Muricata (Graviola) is a 

fruit tree native to North and South 

America and the Caribbean, where it is 

known by such names as Paw-Paw, 

Soursop, and Guanabana. The species 

native to South America is the Guanabana 

tree, and it is prized for its fruit, which is 

used in drinks, ice cream, and 

marmalades. The leaves and seeds of the 

tree have long been used by native 

Accepted 21 st Feb, 2013 

peoples for an astounding variety of 

ailments, ranging from parasites (the 

seeds), to high blood pressure and 

cancer. 

Research on Graviola tree began in 

1940s. In the 1970s with the screening of 

thousands of plants by the National 

Cancer Institute. Initial screening 

demonstrated cytotoxicity against cancer 

cells by several Annona species. In the 

1990s an upsurge in interest is the use of 

herbs to improve health & in new drug 

discovery from natural products spread 

throughout the world. 

Scientific research has validated 

through animal studies the use of various 

parts of the graviola (guanabana) tree for 

hypertension, as a vasodilator, as an 

antispasmodic (smooth muscle relaxer), 

Mishra et al. 1613


and as cardio depressant (slowing of 

heart rate). 

Common Names 

Soursop, Paw-Paw, Graviola, 

Guanabana, Adunu, Sorasaka, Mullaatha, 

Thorny custard apple, Shul-ram-fal, 

Hanuman fal. 

Plant profile 

Kingdom : Plantae 

Division : Angiosperms 

Class : Magnoliids 

Order : Magnoliales 

Family : Annonaceae 

Genus : Annona 

Species : A. Muricata 

Traditional Ethnobotanical Uses 

For diarrhea (fruit), cough, 

hypertension, rheumatism, tumors, 

cancer, asthma, childbirth, lactagogue 

(fruit), malaria, tranquillizer, skin 

rashes, parasites, worms liver 

problems, arthritis(used externally) 13 . 

Traditionally, the leaves are used for 

headaches, insomnia, cystisitis, liver 

problems, diabetes and as anti- 

inflammatory, antispasmodic and anti- 

dysenteric. The decoction of the leaves 

have parasiticide, anti- rheumatic and 

neuralgic effects when used internally, 

while the cooked leaves , applied 

topically, fight rheumatism and 

abscesses 10 . 

Description 

Soursop (Annona muricata) is a 

broadleaf, flowering, evergreen tree native 

to Mexico, Cuba, Central America, the 

Caribbean andnorthern SouthAmerica 

Colombia, Brazil, Peru and Venezuela. 

Soursop also grows in sub-Saharan 

African countries that lie within the tropics. 

Today, it is also grown in some areas 

of Southeast Asia as well as in some 

Pacific islands. It was most likely brought 

from Mexico to the Philippines by way of 

the Manila-Acapulco galleon trade. It is in 

the same genus as the chirimoya and the 

same family as the pawpaw. 

The soursop is adapted to areas of 

high humidity and relatively warm winters; 

temperatures below 5°C (41 °F) will cause 

damage to leaves and small branches, 

and temperatures below 3°C (37 °F) can 

be fatal. The fruit becomes dry and is no 

longer good for concentrate. 

Cultivation 

The plant is grown as a 

commercial crop for its 20–30 cm (7.9–12 

in) long, prickly, green fruit, which can 

have a mass of up to 2.5 kg (5.5 lb). 

Away from its native area, there is some 

limited production as far north as 

southern Florida within USDA Zone 10; 

however, these are mostly garden 

plantings for local consumption. It is also 

grown in parts of Southeast Asia and 

abundant on the Island of Mauritius. The 

soursop will reportedly fruit as a container 

specimen, even in temperate climates, if 

protected from cool temperatures 

Chemical constituents 

Among the chemical constituents found 

in A. muricata, the alkaloids (reticulin, 

coreximine, coclarine and anomurine) and 

Mishra et al. 1614


essential oils (β-caryophyllene, δcadinene, 

epi-α-cadinol and α-cadinol) 

stand out. However, species of the 

Annonaceae family, including A. muricata, 

have also been targeted for investigation 

due to appurtenant substances in the 

acetogenins class that have been isolated 

from different parts of the plant. For 

example, annomuricins A and B, 

gigantetrocin A, annonacin-10-one, 

muricatetrocins A and B, annonacin, 

goniothalamicin, muricatocins A and B, 

annonacin A, (2,4-trans)-isoannonacin, 

(2,4-cis)-isoannonacin, annomuricin C, 

muricatocin C, gigantetronenin, 

annomutacin, (2,4-trans)-10R-annonacin- 

A-one, (2,4-cis)-10R-annonacin-A-one, 

annopentocins A, B and C, cis- and transannomuricin-D-ones, 

annomuricine, 

muricapentocin, muricoreacin and 

murihexocin C and annocatacin A and B 

were identified in the leaves. These 

acetogenins have cytotoxic properties 

against tumor cell lines and molluscicidal 

activity. In addition, A. muricata leaf 

extracts have antioxidant and 

molluscicidal properties 10 . 

BIOLOGICAL PROPERTIES 

Anti-bacterial activity 

The antibacterial effect of the leaves 

of Annona muricata was evaluated on 

bacterial strains like Staphylococcus 

aureus , Escherichia coli , Proteus 

vulgaris , Streptococcuspyogenes, Bacillu 

s subtilis ATCC 12432, Salmonella 

typhimurium, Klebsiella pneumonia No.& 

Enterobacter aerogenes No.2340.The 

solvents used for the extraction of plants 

were water and methanol. The in vitro 

antibacterial activity was performed by 

agar cup method. The most susceptible 

Gram-positive bacteria was B. 

subtalis and S.aureus while the most 

susceptible Gram-negative bacteria 

was K. pneumoniae and P. vulgaris. The 

significant antibacterial activity of active 

extracts was compared with the standard 

antibiotic, streptomycin (100 ppm).The 

results obtained in the present study 

suggest that Annona muricata can be 

used in treating diseases caused by the 

test organisms. 

Anti –Cancer activity 

CANCER is the abnormal growth of cells 

in our bodies that can lead to death. 

Cancer cells usually invade and destroy 

normal cells. These cells are born due to 

imbalance in the body and by correcting 

this imbalance, the cancer may be 

treated 7 . 

Seven new annonaceous 

acetogenins, muricins A−G (1−7), as well 

as five known compounds, a mixture of 

muricatetrocin A (8) and muricatetrocin B 

(9), longifolicin (10), corossolin (11), and 

corossolone (12), were isolated from the 

seeds of Annona muricata. The structures 

of all isolates were elucidated and 

characterized by spectral and chemical 

methods. These acetogenins showed 

significantly selective in vitro cytotoxicities 

toward the human hepatoma cell lines 

Hep G2 and 2,2,15 9 . 

The leaves, bark and stems of 

Graviola, an evergreen indigenous to 

tropical areas in South and North America 

including the Amazon, show remarkable 

cytotoxicity and selectivity against cancer 

cells. The phytochemical group, 

Mishra et al. 1615


Annonaceous acetogenins, seems to play 

a significant role in this tree's antitumor 

properties71-74 . In 1976 plant screening 

program by the National Cancer Institute, 

graviola leaves and stem showed active 

cytotoxicity against cancer cells and 

researchers have been following up on 

these findings since 1975. Much of the 

cancer research on graviola focuses on a 

novel set of phytochemicals called 

Annonaceous acetogenins. Graviola 

produces these natural compounds in its 

leaf and stem, bark, and fruit seeds. Three 

separate research groups have isolated 

these acetogenin compounds in graviola 

which have demonstrated significant 

antitumorous and anticancerous 

properties, and selective toxicity against 

various types of cancer cells (without 

harming healthy cells) publishing eight 

clinical studies on their findings. Many of 

the acetogenins have demonstrated 

selective toxicity to tumor cells at very low 

dosages—as little as 1 part per million. 

Four studies were published in 1998 

which further specify phytochemicals and 

acetogenins which are demonstrating the 

strongest anticancerous, antitumorous, 

and antiviral properties. Thus far, specific 

acetogenins in graviola have been 

reported to be selectively toxic to these 

types of tumor cells: lung carcinoma cell 

lines; human breast solid tumor lines; 

prostate adenocarcinoma; pancreatic 

carcinoma cell lines; colon 

adenocarcinoma cell lines; liver cancer 

cell lines; human lymphoma cell lines; and 

multi-drug resistant human breast 

adenocarcinoma. The group of 

compounds found in Graviola are potent 

inhibitors of NADH: ubiquinone 

oxidoreductase, which is an essential 

enzyme in complex I leading to oxidative 

phosphorylation in mitochondria. They 

also inhibit the ubiquinone-linked NADH 

oxidase enzyme, which is specific to the 

plasma membranes of cancerous cells 1 . 

Other activities 

Many bioactive compounds and phyto 

chemicals have been found in graviola, as 

scientists have been studying its 

properties since the 1940s. Its many uses 

in natural medicine have been validated 

by scientific research. Several studies by 

different researchers demonstrated that 

the bark as well as the leaves had hypo 

tensive, antispasmodic, Anti convulsant, 

vasodilator, smooth muscle relaxant, and 

cardio depressant activities in animals. 

RECENT ADVANCES 

Recent advances in Annonae Research 

As per, The Journal of Natural Products 

(1999), The Annonaceous acetogenins 

are promising new Anti-tumor and 

pesticidal agents that are found only in the 

plant family Annonaceae. Chemically, 

they are derivatives of long chain fatty 

acids. Biologically, they exhibit their potent 

bioactivities through depletion of ATP 

levels via inhibiting complex 1 of 

mitochondria and inhibiting the NADH 

oxidase of plasma membranes of tumor 

cells. Thus they show ATP driven 

resistance mechanism. 

Three different research groups 

have conducted mechanism of action 

studies on Annonaceous acetogenins 

and have confirmed that these chemical 

compounds are highly effective inhibitors 

Mishra et al. 1616


of complex 1 in mitochondrial electron 

transport systems in tumors. Many of the 

acetogenins have a cytotoxicity with ED50 

values as low as 10-9 micro gram / ml. In 

the study conducted by separate research 

groups all have confirmed significant Antitumor, 

Anti- cancer and selective toxicity 

against several different types of cancer 

cells which they studied. 

Recent Advances in Annonaceous 

Acetogenins (National Cancer Institute, 

1997) 

“Annonaceous acetogenins are waxy 

substances consisting of C32 or C34 long 

chain fatty acids which have been 

combined with a 2-propanol unit at C-2 to 

form a lactone. They are only found in 

several genera of the plant family, 

Annonaceae. Their diverse bioactives as 

antitumor, immunosuppressive, pesticidal, 

anti-protozoal, anti-helmentic and 

antimicrobial agents have attracted more 

and more interest worldwide. Recently, we 

reported that the Annonaceous 

acetogenins can selectively inhibit the 

growth of cancerous cells and also inhibit 

the growth of adriamycin resistant tumor 

cells. 

Although most of the acetogenins 

have high potencies among several solid 

human tumor cell lines, some of the 

derivatives within the different structural 

types and some positional isomers 

showed remarkable selectivities among 

certain cell lines (e.g. prostate cancer-3). 

Acetogenins are potent inhibitors of 

NADH; uniquinone oxidoreductase. 

A recent report showed that act directly at 

the uniquinone –catalytic sites within 

complex 1 and in microbial glucose 

dehydrogenase. They also inhibit the 

uniquinone- linked NADH oxidase that is 

peculiar to the plasma membrane of 

cancerous cells. 

CONCLUSION 

Many bioactive compounds and 

phytochemicals have been found in 

graviola, as scientists have been studying 

its properties since the 1940s. Its many 

uses in natural medicine have been 

validated by scientific research. Several 

studies by different researchers 

demonstrated that the bark as well as the 

leaves had hypotensive, antispasmodic, 

anticonvulsant, vasodilator, smoothmuscle 

relaxant, and cardiodepressant activities 

in animals. The phytochemical group, 

Annonaceous acetogenins, seems to play 

a significant role in this tree's antitumor 

properties. Much of the cancer research 

on graviola focuses on a novel set of 

phytochemicals called Annonaceous 

acetogenins. Graviola produces these 

natural compounds in its leaf and stem, 

bark, and fruit seeds. Three separate 

research groups have isolated these 

acetogenin compounds in graviola which 

have demonstrated significant 

antitumorous and anticancerous 

properties, and selective toxicity against 

various types of cancer cells.Therefore it 

can be concluded that Chemopreventive 

agents are much sought after as an early 

interventional approach to prevent tumor 

development or to lower the incidence risk 

of cancers. Given that the current 

available methods of treatment are 

chemotherapy, radiation, and surgery, all 

of which can induce significant side 

Mishra et al. 1617


effects, an urgent need for alternate or 

adjuvant therapies has arisen. 

Phytochemicals are relatively safe and 

abundantly available from dietary sources. 

Therefore, alternate medicine aims at 

harnessing the protective properties of 

these nonessential nutrients toward 

cancer prevention and treatment. 

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Fig. no. 1 Leaves and fruit of Annona 

muricata 

Mishra et al. 1618

Annona muricata (The cancer killer): A review

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