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Annona muricata has been attributed with numerous health benefits – including anticancer properties. The aim of this study was to carry out anticancer. Annona muricata L. (A. muricata) is a species of the Annonaceae family that has been . The increasingly popular use of A. muricata as an anticancer treatment. Extensive anticancer investigations have been conducted on A. muricata due to its reported ethnomedicinal uses against.

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The incidence of cancer is muicata each year, which generates concerns regarding the efficacy of the current treatment options. This has caused patients to seek annoona to complement or to replace surgery, chemotherapy and radiotherapy. Annona annonq and other plants have been shown to have promising compounds that can be utilised in the treatment of cancer. Native to the tropical and subtropical parts of the world, A.

In light of increasing concerns regarding the limitations of cancer treatment in hospitals, this review attempts to highlight the benefits of A. Cancer, including breast cancer, has become a major health concern worldwide. It is estimated by the World Health Organization WHO that in the period between and84 million deaths would be attributed to cancer 2.

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In the United States, an estimate shows that approximatelydeaths will occur among Americans in the year due to cancer, with the most common including the lung, prostate and colorectum in men and the breast, bronchus and colorectum in women 3.

In Malaysia, a similar trend was muriicata observed. Based on the latest press statement by the Director General of Health Malaysia, of all deaths in hospitals linked to the Ministry of Health Malaysia, cancer has contributed to The press statement also reported that inthe trend in terms of most common cancers remained consistent, as reported by Zainal 4. The five most common cancers in the Malaysian male population are colorectum, lung, nasopharynx, lymphoma and prostate cancers, whereas in Malaysian female, the most common cancers are breast, colorectum, cervix uteri, ovary and lung cancers.

Although major breakthroughs have been achieved in the field of surgery, chemotherapy and radiotherapy, many still express concerns regarding these methods of treatment due to their limitations and, most noticeably, their side effects. Conventional 3D radiation therapy has been shown to be effective in the treatment of head and neck cancers, but the side effects that follow often cause discomfort and reductions in the quality of life among patients. Such side effects include xerostomia, which results in weight loss, and prolonged infections within the oral cavity and dental cavities 6.

Although the development of intensity modulated radiotherapy IMRT to replace conventional radiation therapy allows the parotid glands to be spared 7 and results in an overall increase in the quality of life of patients 8exposure to high doses of IMRT radiation reportedly causes dysphagia in patients 9. Apart from the obvious toxicity induced by chemotherapy, another side effect that might appear following radiotherapy is hypothyroidism.

Chemotherapy is also considered to be hazardous when administered to older patients. A study conducted by the Southwest Oncology Group on the induction of neuropathy in patients aged 65 years old and above showed an increase in the incidence of neuropathy in patients due to the toxicity of the taxane-based chemotherapy agent. The incidence of neuropathy was also shown to be particularly higher in patients diagnosed with diabetes Cisplatin is another example of a chemotherapy agent that is associated with negative side effects in patients diagnosed with malignancies.

Furthermore, cisplatin was also shown to be responsible in the generation of mutated red blood cells, and it was further suggested that such observation might be because of stem cells mutagenesis These issues, among others, have created a significant distrust towards cancer management procedures in hospitals and have caused patients to seek treatment elsewhere, especially from traditional medications, whether as a complementary treatment alongside conventional medications or as a way to improve their health without the treatments offered by hospitals.

Although these traditional medications pose many issues regarding toxicity and efficacy due to the lack of high-quality studies, these remedies should not be completely left out as potential treatments. Based on cell cultures and animal studies, multiple bodies of evidence have been put forward in the scientific community regarding the potential use of traditional medications as a means to treat illnesses, including cancer. In this review, we explore some of the benefits of complementary and alternative medicines CAMsparticularly Annona muricataas potential treatments agent against breast cancer and other forms of cancer.

Complementary and alternative medicine is defined as means of treatment that are outside the scope of modern medicinal treatment. These treatments may be used as therapeutic and preventative agents to assist in combating physical or mental illnesses.


They have been widely used for generations to treat illnesses prior to the arrival of modern medicine. Since the establishment of modern medicine, CAM has been used in conjunction with current treatment methods in certain countries to help and assist patient recovery These types of treatments include natural products supplements, such as fish oil; body practices, such as yoga, Tai Chi or Qigong; and mind relaxation techniques, such as meditation and hypnotherapy In recent years, CAM has become more popular among the public, especially among cancer patients.

In addition to benefits in terms of improving the health of users, the ingredients used in CAM that are usually extracted from resources such as plants and animals are assumed to be safe for consumption.

Another major attraction of CAM is anticancee the source materials are cheap and readily available or easily planted for personal use. More importantly, the invasive procedures and adverse effects associated with medical treatments such as radiotherapy and chemotherapy often lead many to seek CAM as their main source of treatment. In Malaysia, CAMs are also sought due to their benefits in improving health.

More importantly, these CAMs have been used and practiced traditionally for centuries among Malaysians. A nationwide study conducted to examine the popularity of CAM in the Malaysian population revealed that the majority of Malaysians who participated in the study have used therapies that were biologically based for solving health issues and for improving and maintaining overall health The tropical plant is characterised as an evergreen and flowering tree that can stand up to 8 metres xnnona and that produces edible fruits Most parts of the plant are used in traditional medications in treating various diseases and ailments see Figure 1including inflammation 33rheumatism 29diabetes 1hypertension 34 and parasitic infestation Benefits of Annona muricata extracts in the treatment of illnesses 1.

The seed is extracted and used to fight against worms, while the fruits are used traditionally to cure arthritis and fever. Both the seeds and fruits are also used to treat parasitic infections.

Oxidative Medicine and Cellular Longevity

The leaves are used as a traditional medication to fight against collapses 36hypoglycaemia, inflammation and as a relief medication against spasms The plant has been used widely as a source of chemically active metabolites due to their various curative properties 28 and is thus considered as a good candidate to be used as a complementary medicine.

A phytochemical composition analysis of A. These compounds are called Annonaceous acetogenins AGEswhich were shown to induce cell cytotoxicity by inhibiting the mitochondrial complex I Other studies have also suggested the presence of compounds such as megastigmanes 40cyclopeptides and essential oils 4142as well as essential minerals, such as K, Ca, Na, Cu, Fe and Mg A study by George also showed great potential for the use of A. The study showed that the n-butanolic leaf extract of A.

Within the compounds that were isolated from different parts of the plant, acetogenins AGEs were reported to be the major phytochemicals, followed by alkaloids and phenols These secondary metabolites were first isolated from multiple parts of plants belonging to the Annonaceae family in by Tempesta, and acetogenins were further determined to have toxicity towards the P lymphocytic leukaemia in mice Since their discovery, more than AGEs have been discovered from different parts of the plant 1.

Multiple forms of AGEs have been studied for their mechanisms that can be used against particular targets, such as insects and tumour cells.

Acetogenins have been shown to be very effective against insects and can be used as insecticides and insect repellent. Multiple parts of the plant, including the roots, leaves, unripe fruits and seeds, have been shown to have insecticide and insect repellent properties 5152 Further tests using lower concentrations of the ethanolic extracts even showed an ability to significantly reduce the survival of the larvae population Crude extracts from the plant were also shown to be effective against Aedes aegyptiin combination with silver nanoparticles, which makes A.

A similar anti-parasitic effect was also observed when methanolic extracts of the seed were used against Entamoeba histolticaMolinema dessetae and Artemia salinawhich was later deduced to be due to the presence of acetogenins The role of acetogenins in inhibiting the growth of insect larvae was suggested to be due to the THF ring inhibition of the mitrochondrial complex I through NADH oxidase inhibition The capacity of acetogenins to inhibit NADH oxidase was also shown to be important for their anti-tumour function.

The report suggested that exposure to an acetogenin called bullatacin specifically inhibited NADH oxidase enzyme functions isolated from Hela cells as HL cancer cells Acetogenins were also shown to be capable of blocking ATP production in mitochondria. This mechanism of action was shown to be effective against cancer cells that produce higher amounts of ATP in comparison to normal cells, thus limiting the ability of cancer cells to grow Interestingly, AGE toxicity was observed in the cancer cells, with a minimal negative impact on the normal cells.


Studies using AA mimetics have suggested that acetogenin analogues synthesised in vitro have shown toxicity towards the HCT-8 and HT29 cell lines, with negative toxicity towards the normal human cell line HELF Similarly, a study using A. These observations thus suggest the potential antiicancer of AGEs as treatment options against cancer.

A dysfunctional apoptotic pathway is one of the main contributors to carcinogenesis. The inability of cells to execute apoptosis to remove cancer cells was observed in multiple cancer types, including breast, pancreatic, ovarian and colorectal cancers 61 — This occurrence creates imbalances between cell proliferation and cell death and can be caused by disruptions in the normal functions of the apoptotic pathway.

Similar to other types of cancer, failure to carry out apoptosis in breast cancer cells might be attributed to the disruptions within the apoptotic pathway.

Defects within the intrinsic pathway, for example, have been associated with the progression of breast cancer.

Potential Benefits of Annona muricata in Combating Cancer: A Review

Defects in the regulation of cytochrome release 66apoptosome formation 67 and caspase activation 68 have all been shown to be present within breast cancer cells. The capability of inducing cancer cell cytotoxicity has been one of the main reasons behind the increased interest among scientists in the benefits of CAM, especially plant-based CAMs. Such a potential was also evident in the prevention of skin papillomagenesis in laboratory mice.

In this study, ethanolic extracts of A.

Anticancer Properties of Graviola (Annona muricata): A Comprehensive Mechanistic Review

In terms of specific effects against breast cancer, several studies have indicated the potential use of this plant in potential therapeutic treatments in patients. Gomes further reported that A. A separate study by Rachman showed that the ethanol extracts of leaves of the soursop plant extracted into ethanol induce cytotoxic activity within the breast cancer cell line MCF7 Another murciata by Gavamukulya anticxncer showed that a similar ethanol extract of the soursop plant leaves was found to be highly cytotoxic in vitro against the two human breast cancer cell lines MDA and SKBR3 The growth and viability of the liver cancer cell HepG2 was muticata to be inhibited following incubation with an ethanol extract of A.

The cytotoxic effect observed in the HepG2 cell line was suggested to be a result of induction of the apoptosis pathway through the production of reactive oxygen species ROS In a aticancer study using a similar cell line, Liu 74 also demonstrated the capability of A.

A bioinformatic analysis of the up-regulation of these proteins suggested that the treatment of HepG2 cells with A. Graviola leaf extract GLEflavonoid-enriched extract and acetogenin-enriched extract AEF administered amnona vivo and in vitro were also shown to negatively affect muricataa proliferation of prostate cancer.

This study not only showed the efficacy of A. A similar study also revealed that the treatment of pancreatic cancer cells with A. Thus, the inhibition of these pathways is in agreement with the decreased viability of pancreatic cancer cells treated with the plant extract A study performed on pancreatic cancer cells by Torres showed that annina migratory capacity of pancreatic cancer anjona was reduced after treatment with a graviola extract, as evaluated by a transwell assay, suggesting that the natural extract reduces the motility of pancreatic cancer cells.

The motility and migration of cancer cells is associated with the arrangements of the cortical actin and microtubules network. Additionally, cellular ATP depletion has been associated with muicata reorganisation of the actin cytoskeleton and a suspension of the dynamics of microtubules, which is known to induce mitotic arrest.

Thus, graviola extracts cause a disruption of the cortical actin network that can inhibit the motility of cancer cells Moghadamtousi showed that A. This finding was confirmed by high-content screening HCS multiple cytotoxicity analyses that examined the characteristics of apoptosis before and after treatment with A. The analyses showed that A murifata treated with A. Cancer is a disease caused by cell cycle dysfunction.

The ability to block the cell cycle progression in cancer cells can effectively elevate the anti-cancer potential of natural products The study also showed that treatments of HCT and HT cells resulted in the up-regulation of the apoptotic pathway, as suggested by an increase in the production of ROS, an increase in detectable cytochrome cand an increase in initiator and executioner caspases in both of the tested cell lines.