INTRODUCTION:

Annona muricata is another name for soursop. This fruit, called the soursop or Lakshman Phal in India, is native to Brazil. For cancer patients, it functions like a miracle and is regarded as a gift from God to humanity. It is full of nutrients and a great source of antioxidants. Fruits have always been essential to a human diet. In addition to being viewed as dietary supplements, they are widely accepted as being crucial to people's wellness. In addition, fruits are high in carbohydrates, moisture, and organic, inorganic, and bioactive substances.^1,2. Since the beginning of medicine, natural products, especially those made from plants, have been used to support human health. Plant phytochemicals have been a key source of new medicinal discoveries over the past hundred years.

The biological activities of such compounds require significant research due to the importance of plant-active components in agriculture and medicine.³ There arearound 119 distinct species of this fruit that may be found worldwide. There are seven species and one hybrid of these at the moment. Fruit is grown naturally all over the world.⁴ Fruits can contain anywhere from five to hundreds of seeds. Short spines in the skin resemble circulated leather. A multitude of white, fibrous, juicy segments surround a soft, bitter core that can easily be separated from the cream-colored, granular inner surface. Three broad categories are used to categorize Puerto Rican seedling soursops: sweet, acid, and mixed. They are finally divided into four categories: round, heart-shaped, oblong, and angular. These divisions are based on the type of flesh, which can be firm and slightly dry or soft and juicy. Annona muricata, commonly referred to as Soursop or Graviola, is a tropical fruit-bearing tree with a rich and diverse history of use in ethnomedicine spanning thousands of years. Although it is native to tropical regions of Central and South America, its medicinal qualities, economic worth, and cultural significance have led to its widespread cultivation and use throughout the world, including the Caribbean, southern Florida, and Southeast Asia. The plant is a goldmine of bioactive substances, such as acetogenins, which have been shown in studies to exhibit strong anti-tumor activity. These compounds work by preventing the growth of different types of cancer cells by specifically targeting NADH oxidase, an enzyme that is essential to the metabolism of cancer cells. Due to its numerous pharmacological activities, including cytotoxic, antileishmanial, wound-healing, antimicrobial, and anti-inflammatory properties, Annona muricata is a valuable adjunct for both traditional medicine and modern therapies. According to phytochemical analysis, it contains a number of bioactive compounds, such as cardiac glycosides, tannins, steroids, and alkaloids, which are responsible for its medicinal properties and the possibility of developing new drugs and treatments.⁵

Biological Source:

The tropical plant known as soursop, which is indigenous to Central and South America, is descended from Annona muricata. Reaching upwards of ten meters in height, this deciduous tree or shrub has glossy, dark green leaves with a broad crown. For centuries, traditional medicine has used the plant's leaves, fruits, seeds, bark, and roots to treat a variety of ailments, such as cancer, infections, oxidative stress, and inflammation.

Bioactive substances including glycosides, alkaloids, and acetogenins, which have anti-inflammatory, anti-cancer, and antimicrobial qualities, are found in the leaves of the soursop plant. The fruit itself is a healthy snack because of its soft, creamy interior and abundance of nutrients, minerals, and antioxidants. The alkaloids and acetogenins found in the seeds are noteworthy because they have insecticidal and pesticidal qualities. Furthermore, the plant's roots and bark are abundant in bioactive substances with antibacterial and anti-inflammatory properties. With so many applications and health advantages, this adaptable plant has been a priceless resource for centuries. It is an important plant for both traditional medicine and contemporary uses because its various parts have historically been used to treat serious illnesses and improve general health.

"Alternative names for Soursop include Annona Macrocarpa Wercle. This species belongs to the:

· Kingdom: Plantae - This indicates that Soursop is a plant, which is one of the six kingdoms of life.

· Clade: Magnoliids - This clade includes a group of flowering plants known as magnoliids, which are characterized by their advanced floral structures.

· Order: Magnoliales - This order includes several families of flowering plants, including the Annonaceae family to which Soursop belongs.

· Family: Annonaceae - This family is commonly known as the custard apple family and includes several genera of flowering plants, including Annona.

· Genus: Annona - This genus includes several species of flowering plants, including Soursop (Annona muricata), which is also known by its synonym Annona Macrocarpa Wercle.

The species Annona muricata is an evergreen terrestrial tree with upright branches and glossy, dark green leaves that can reach a height of between five and eight meters. The canopy of the tree is open and rounded in some places. On woody stalks known as pedicels, it bears large, lone yellow flowers. The three large, broadly ovate outer petals of these yellowish or greenish-yellow flowers have a heart-shaped base. Additionally big, elliptical, and round are the inner three petals. The tree produces big, edible green fruits called "souropsop," which can be heart-shaped, oval-shaped, or asymmetrically lopsided at times. These fruits range in diameter from fifteen to twenty millimeters and can weigh more than 4 kilograms of weight. The pulp of the fruit is made up of elongated, fibrous, juicy segments that surround a white core. Each fertile segment contains a single oval, smooth, hard black seed, measuring between 1/2 and 3/4 inches (1.25 to 2 centimeters) in length. The soursop tree can grow up to 8 to 10 meters in height and has a structure with erect branches that are low to the ground. Its leaves are glossy and remain green throughout the year.⁶

Annona muricata, the soursop, and the bioactive substances that it contains:

1. Acetogenins:

· (Annonaceous acetogenins) from leaves: They have antibacterial properties, trigger cell death, and stop the spread of cancer cells.

· Alkaloids: Reticuline and anthine: Display anti-inflammatory, antimicrobial, and antioxidant characteristics.

· Glycosides: Display antibacterial and anti-inflammatory qualities (annonacosides).

2. Fruits:

· Vitamins (C, B6, and B12): These are essential for energy metabolism, immunological response, and nerve function.

· Minerals: Iron, magnesium, and potassium are necessary for heart health, muscle contraction, and the transportation of oxygen.

· Antioxidants (flavonoids, phenolic acids): Protect against oxidative stress, inflammation, and cancer.

3. Seeds:

· Acetogenins (annonaceous acetogenins): Demonstrated to possess insecticidal characteristics, trigger programmed cell death, and impede the proliferation of cancer cells.

· Alkaloids: Reticulon and annine: Show anti-inflammatory, antimicrobial, and antioxidant characteristics.

4. Bark:

· Alkaloids (reticuline, annine): Shown to have antioxidant, antimicrobial, and anti-inflammatory properties.

· Glycosides (annonacosides): Exhibit anti-inflammatory and antimicrobial properties.

5. Roots:

· Acetogenins (annonaceous acetogenins): Show antibacterial activity, induce apoptosis, and inhibit the growth of cancer cells.

· Soursop (Annona muricata) is an evergreen tree that exhibits fast growth, reaching up to 1 meter per year. It can thrive in various environments and tolerate drought, but prefers consistent moisture. The tree reproduces via seeds, cuttings, and grafting, producing small, yellowish-green flowers and prickly, green fruit with numerous black seeds.

Physiologically, soursop is a C3 plant with high stomatal density, moderate to high water requirements, and temperature tolerance between 15-35°C (59-95°F). Biochemically, it is rich in bioactive compounds, including acetogenins, alkaloids, flavonoids, terpenoids, glycosides, and phenolic acids, which contribute to its anticancer, antimicrobial, anti-inflammatory, and antioxidant activities.

Genetically, soursop is a diploid species (2n=2x=14 chromosomes) with moderate to high genetic diversity and an approximate genomic size of 450 Mbp (megabase pairs). Ecologically, it relies on insects and wind for pollination, animals and water for dispersal, and forms symbiotic relationships with fungi, bacteria, and insects. Soursop occupies a unique ecological niche in tropical forests, woodlands, and coastal areas, making it a valuable resource for various applications.

Fig. 2: SOURSOP

Chemical Constituents:

The fruit of Annona muricata contains a variety of substances and secondary metabolites. Acetogenins, alkaloids, flavonoids, essential oils, vitamins, carotenoids, amides, and cyclopeptides are the main constituents. The substances aluminum chloride, calcium chloride, potassium chloride, magnesium chloride, potassium bromide, sodium sulfate, sodium bicarbonate, dimethylsulfoxide, potassium ferrocyanide, ferric chloride, sodium carbonate, Folin-Ciocalteu reagent, trichloroacetic acid, sodium chloride, dichloromethane, hexane, butanol, methanol, ethanol, pyridine, 2,2-Diphenyl-1-Picrylhydrazyl (DPPH), linoleic acid, β-carotene, tween 40, Butylated Hydroxytoluene (BHT), rutin, gallic acid, caffeic acid, 5-caffeoylquinic acid, acarbose, orlistat, pancreatic lipase, pancreatic α-amylase α-glycosidase and ascorbic acid.^7-8

The chemical components of annona muricata, or soursop, and their possible effects:

1. Acetogenins:

Soursop belongs to the Annonaceae family, which is home to a special class of compounds known as acetogenins. Their polyketide structure distinguishes them as long-chain fatty acids. Important acetogenins found in soursop include:

One of the acetogenins that has been researched the most is annonacin. It can kill cancer cells in a lab setting because it has been demonstrated to have strong cytotoxic properties. Its possible neurotoxic effects, especially at high doses or with prolonged exposure, are also linked to it, which raises questions about its safety when consumed regularly in food.

Annonacin A: An additional powerful acetogenin with annonacin-like biological activities and concerns, and a structure similar to annonacin.

The mitochondrial complex I, a component of the Acetogenins inhibit the electron transport chain's mitochondrial complex I. Cell death results from this action's decrease in ATP production. Because neuronal cells depend primarily on mitochondria for energy, acetogenins present risks to them even though this property makes them interesting for use in cancer research.

2. Alkaloids:

Alkaloids are nitrogen-containing substances that are frequently recognized for their pharmacological actions. Several alkaloids found in soursop have been identified.

Annonamine is an alkaloid whose possible bioactive qualities, such as antibacterial and anti-inflammatory effects, have been investigated.

Analogously to annonamine, coreximine has demonstrated possible biological activities; however, there is currently a dearth of research elucidating its precise mechanisms.

Alkaloids found in Annona muricata: total chemical structure:

1. Aphorphine

2. Protoberberine

3. Iminosugar

4. Isoquinoline

A) Aphorihine type B) Protoberberine type

C) Iminosugar type D) Isoquinoline type

3. Flavonoids:

Strong antioxidant qualities are exhibited by flavonoids, which are polyphenolic compounds. They aid in lowering oxidative stress and neutralizing free radicals. Among the major flavonoids found in soursop are:

Known for its anti-inflammatory, antiviral, and anticancer effects, quercetin is an antioxidant. It assists in lowering the risk of long-term conditions like cancer and heart disease.

Kaempferol: An additional flavonoid possessing potent antioxidant properties. Studies have been conducted on its capacity to shield cells from.

4. Tannins:

One class of polyphenol with astringent qualities is tannins. They can have antibacterial and anti-inflammatory properties in addition to boosting soursop's antioxidant content.

5. Essential Oils:

Several volatile compounds are present in the essential oils that are extracted from the leaves and seeds of soursop, including:

One sesquiterpene with analgesic and anti-inflammatory qualities is beta-caryophyllene. Its potential therapeutic effects are further enhanced by its ability to function as an agonist of cannabinoid receptors.

Alpha-pinene: Well-known for its bronchodilator, antibacterial, and anti-inflammatory qualities.

Linalool is a flowery-scented terpene that has sedative and calming properties. It has antimicrobial qualities as well.

6. Minerals and Vitamins:

· Vitamin C: Rich in antioxidant defense, strong immunity, and healthy skin, soursop is a good source of this essential vitamin. The B vitamins—niacin (B3), folic acid (B2), and vitamin folate (B9)—are crucial for energy metabolism, DNA repair, and neurotransmitter synthesis.

· Calcium: An essential mineral that supports blood pressure regulation, fluid balance, and muscle contraction control. The health of bones, muscles, and enzyme activity depend on magnesium and calcium.

7. Fiber and Carbohydrates:

· Sugars: Fructose and glucose, two naturally occurring sugars found in the fruit, provide a rapid energy boost.

· Dietary fiber: Soursop has soluble and insoluble fibers, both of which are beneficial to the health of the digestive system. They can assist in controlling cholesterol levels and help to maintain bowel regularity.

8. Lipids:

Lipids, particularly fatty acids, are abundant in soursop seeds.

Skin and cell membrane health are greatly dependent on linoleic acid, an important omega-6 fatty acid. Additionally, it has an impact on immunological and inflammatory responses. The numerous potential health advantages of soursop, such as its antimicrobial, antioxidant, and possibly anticancer qualities, are a result of these compounds. Nonetheless, consumption must be done so with caution due to certain compounds, such as acetogenins, especially in light of potential neurotoxic effects. Before using soursop for medicinal purposes, especially in large quantities or as extracts, it is always advisable to speak with healthcare professionals.

Geographical source:

The tropical regions of Central and South America, namely Mexico, Costa Rica, Panama, Colombia, Venezuela, Ecuador, Peru, and Bolivia, are home to the soursop (Annona muricata). It can also be found in the Caribbean islands of Trinidad and Tobago, Jamaica, Puerto Rico, Cuba, and Hispaniola (which includes Haiti and the Dominican Republic). Other tropical and subtropical areas, including Asia (India, Southeast Asia, and the Philippines), the Pacific Islands (Hawaii, Tahiti, and Fiji), and Africa (West, East, and South), have also seen the naturalization and cultivation of soursop.

Soursop is widely distributed in the wild throughout Central America. Limón, Puntarenas, and San José are among the Costa Rican provinces where it grows, and Bocas del Toro, Chiriquí, and Veraguas are among the Panamanian provinces where it grows. Soursop is a widely distributed vegetable in South America. It grows in departments such as Caldas, Quindío, and Risaralda in Colombia, and in the states of Mérida, Trujillo, and Táchira in Venezuela.

Soursop is a common fruit tree in the Caribbean, growing on many islands. As a result of introduction and naturalization, soursop has spread throughout Africa, growing wild as well as being farmed for its fruit and wood in nations like Ghana, Nigeria, Senegal, and Côte d'Ivoire.

Worldwide Ethnomedical Uses:

· Brazil: The plant is used for treating a variety of conditions including abscesses, bronchitis, chest problems, coughs, diabetes, diarrhea, dysentery, edema, fever, intestinal colic, intestinal parasites, liver problems, neuralgia, nervousness, pain, parasites, rheumatism, spasms, and worms.

· Caribbean: It is applied to address chills, fever, flu, indigestion, nervousness, palpitations, rashes, skin diseases, and to function as a sedative.

· Curaçao: The plant is used for issues related to childbirth, gallbladder problems, nervousness, and also serves as a sedative and tranquilizer.

· Haiti: The plant is employed for various ailments including digestive sluggishness, coughs, diarrhea, fever, flu, heart problems, aiding lactation, lice, nervousness, parasites, pain, pellagra, sores, spasms, weakness, wounds, and serves as a sedative.

· Jamaica: It is used to treat asthma, fevers, heart conditions, hypertension, support lactation, manage nervousness, combat parasites, address spasms, water retention, weakness, worms, and function as a sedative.

· Malaysia: The plant is utilized for boils, coughs, diarrhea, dermatosis, hypertension, rheumatism, and to help reduce bleeding.

· Mexico: It is applied to treat diarrhea, dysentery, fever, chest colds, ringworm, scurvy, and to help reduce bleeding.

· Panama: The plant is used for diarrhea, dyspepsia, kidney problems, and stomach ulcers.

· Peru: The plant is employed for treating diabetes, diarrhea, dysentery, fever, hypertension, indigestion, inflammation, lice, liver disorders, parasites, spasms, tumors, internal ulcers, and also acts as a sedative.

· Trinidad: It is applied for blood cleansing, fainting, flu, high blood pressure, aiding lactation, palpitations, and ringworm.

· U.S.A.: The plant is used for managing cancer, depression, fungal infections, hypertension, intestinal parasites, and tumors.

· West Indies: It is used to treat asthma, support childbirth, manage diarrhea, hypertension, aid lactation, combat parasites, and address worms.

· Elsewhere: The plant is used for conditions such as arthritis, asthma, bile insufficiency, childbirth, cancer, diarrhea, dysentery, fever, heart issues, kidney problems, aiding lactation, lice, liver disorders, malaria, pain, ringworm, scurvy, stomach problems, and also functions as a sedative.⁹

Pharmaceutical Uses:

In the world, cancer ranks as the second most common cause of death. An estimated 12% of all deaths worldwide are attributed to cancer, with over 10 million new cases and 6 million related deaths reported each year¹⁰. It is anticipated that during the next 20 years, the number of new cancer cases will increase by roughly 70%, with over 15 million new cases expected to be diagnosed annually by 2020¹¹. The population is aging and growing, and additional factors contributing to this rapid rise include hormones, infections, genetic mutations, carcinogens, immune system disorders, and the uptake of dietary and behavioral risk factors like smoking, poor diet, inactivity, and environmental pollutants¹². The risk factors have the ability to work alone or in combination to mutate normal cells¹³. The expression or function of important gene products is altered by many of these mutations, which results in uncontrolled cell division and cancer. As of right now, surgery, chemotherapy, radiation therapy, gene therapy, and/or hormonal therapy either alone or in combination are the primary methods used to treat cancer. Chemotherapy medications that target cancerous cells or stop them from proliferating include hormones, antimetabolites, DNA-interacting agents, antitubulin agents, and molecular targeting agents.¹⁴

Many studies are looking into the potential anti-cancer properties of soursop (Annona muricata) and how it might be used to treat cancer. The main points include the following:

· Pancreatic Cancer:

It appears that only 8% of people will survive five years after being diagnosed with pancreatic cancer, the fourth most common cause of cancer-related deaths globally. Late diagnosed patients have a high death rate because they do not exhibit early clinical symptoms. Novel early detection markers, as well as the development of chemo-preventive and chemotherapy agents, have been spurred by late diagnosis, resistance to current chemotherapy treatments, and the highly aggressive nature of cancer. Science has not yet established any of the plant compounds that have been investigated as treatments for pancreatic cancer.¹⁵

· Cancer of the Lungs:

The most frequent cause of cancer-related mortality globally is lung cancer. Chemotherapeutic tolerance causes a large number of lung cancer patients to pass away. Human lung adenocarcinoma cell lines A549 were used in in vitro studies to demonstrate the cytotoxic activity of A. muricata leaf extract. The IC50 values for the hexane, ethyl acetate, and methanol extracts were 21.05±0.42µg/mL, 5.09±0.4µg/mL, and ≥100µg/mL, respectively, causing cell cycle arrest at the G0/G1 phase and apoptosis¹⁶. The compounds cis-gigantetrocinone and trans-gigantetrocinone, cis-iso and cis-Annonacin-A-oneTrans-iso and annonacinThe isolated acetogenins squamolone and annonacin are cytotoxic to A549 cell lines, and the ED50 values

were 3.39 × 10−2. 9.74 × 10−3 4.42 × 10−5, ≥ 10, 1.48 × 10−3 correspondingly.¹⁷

· Prostate Carcinoma:

In Western developed countries, prostate carcinoma is the leading cause of cancer-related advancements in early detection and innovative treatment methods can greatly extend the lives of these patients, a sizable percentage of them develop aggressive, refractory tumors with a poor prognosis. No clinically significant results have been obtained from the use of a number of bioactive compounds as adjuvants to current therapy for the treatment and prevention of hormone-refractory pancreatic cancer.¹⁸

· Breast Cancer:

Breast cancer ranks as the most common cancer among women globally. There is no treatment for advanced breast cancer; however, early-stage breast cancer may be managed. In order to prevent tumor formation and lessen associated morbidity, new chemopreventive and chemotherapeutic medications are urgently needed. Their low clinical efficacy has hindered their translational use, despite the fact that some natural chemicals have been studied in vitro and found to be safer and less hazardous than synthetic compounds¹⁹. Strong antiproliferative and antitumor properties of A. muricata have been shown in recent studies. When A. muricata leaf extract and ethyl acetate fraction were added to cancer cells, the cells underwent morphological changes that were suggestive of apoptosis, which is defined by the rupture and loss of the cell's membrane and heart.²⁰

· Colon Carcinoma:

The third leading cause of cancer-related deaths is colorectal cancer (CRC). Therapeutic resistance and medication toxicity against current treatments are the main issues for patients with colorectal cancer (CRC), and they are linked to a poor prognosis²¹.

· Head and Neck Cancers:

Generally known as head and neck squamous cell carcinoma (HNSCC)²², these cancers are the sixth most common in the world and originate from the mucosal epithelium of the oral cavity, pharynx, and larynx. A number of anticancer medications, including fluorouracil, doxorubicin, topotecan, etoposide, and cisplatin, have been associated with unfavorable side effects that significantly reduce their usefulness. Due to resistance to available chemoradiotherapy, patients with HNSCC have a poor prognosis despite current advancements in the understanding and treatment of the disease. Therefore, it is imperative to look into anticancer compounds with lower toxicity.

· Hematological cancers:

Acute myeloid leukemia, multiple myeloma, non-lymphoma, and B-cell chronic lymphocytic leukemia Worldwide, 4% of cancer diagnoses are Hodgkin's disease. Notwithstanding its biological features and intricacy, the disease presents unique clinical difficulties. After phytocompounds and their derivatives were tested in clinical trials, most of the compounds proved to be ineffective, leading to resistance. For this reason, it is critical to create new natural chemical compounds with enhanced therapeutic potential. Focused investigation into widely used medicinal plants can expedite the development of new anticancer drugs, despite the tedious and costly nature of random screening²³.

· Liver Cancer

It has been demonstrated that plant extracts have a cytotoxic effect on hepatic cancer cells, suggesting that they may be used as a treatment for hepatic cancer. After being incubated with an ethanol extract of A. muricata, it was observed that the HepG2 cell line's growth and viability were inhibited; after 24 and 48hours of treatment, the LD50 values were 180 and 80µg/mL, respectively, and apoptosis was induced by the ROS pathway²⁴.

· Cervical Cancer

Various solvent leaf extracts were able to produce antiproliferative activity in HeLa cervical cancer cells. The proliferation of the HEp-2 (laryngeal cancer) cell line was inhibited by A. muricata methanol leaf extract, as demonstrated by the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazole) (MTT) reduction method²⁵. Later on, though, it was established that HEp-2 was actually a cross-contaminated HeLa cell line²⁶.

CONCLUSION:

Annona muricata, also known as soursop, is an evergreen plant that grows practically everywhere. The extract from Annona muricata has more than 212 distinct phytoconstituents. Annonaceous acetogenins are significant chemical components that are nearly universally present in plants and are linked to a number of health issues in people. The alkaloids, flavonoids, and phenols in this plant have a variety of functions. Apart from being a valuable resource for the food industry and a native medicinal plant, Annona muricata, or soursop, has been shown to exhibit a diverse range of biological activities. While soursop is a nutritious food, all parts of Annona muricata, including the fruit, contain annona-cin, the most abundant acetogenin, which has been shown in experiments to be toxic to dopaminergic and other neurons both in vitro and in vivo. Atypical parkinsonism risk has been associated with fruit consumption, according to epidemiological evidence in a number of global locations.

Due to the anti-tumor, anti-cancer, and anti-metastatic qualities of its constituent parts, soursop fruit has demonstrated impressive potential in the fight against cancer. The pulp, seeds, and leaves of the fruit have been shown to stop cancer cells from proliferating, cause cell death, and stop cancer from spreading to other areas of the body. In particular, the soursop fruit has been investigated for its potential to prevent cancers of the breast, lung, prostate, colon, and pancreas, among other organs. The anti-cancer properties of soursop fruit make it a promising complementary therapy, providing hope to those looking for alternative or adjunct treatments to traditional cancer therapies, though further research is necessary to fully understand its mechanisms and effects.

REFERENCE:

1. J. Ndife, P. J. Kwaya, and S. Bello. Production and evaluation of storage changes in soursop-juice. Asian Journal of Agriculture and Food Sciences. 2014; 2(5).

2. A. Zahid and R. Khedkar. Valorisation of fruit and vegetable wastes: a review. Current Nutrition and Food Science. 2022; 18(3): 315–328.

3. Moghadamtousi SZ, Goh BH, Chan CK, Shabab T, Kadir HA. Biological activities and phytochemicals of Swietenia macrophylla king. Molecules. 2013; 18: 10465-10483

4. C. F. B. Sanchez, B. E. Lopes, P. E. Teodoro et al. Genetic diversity among soursop genotypes based on fruit produc tion. Bioscience Journal. 2018; 34(1): 122–128.

5. Gajalakshmi S, Vijayalakshmi S, Rajeshwari Devi V. Phytochemical and Pharmacological Properties of Annona muricata: A Review. Int J Pharm Sci. 2012; 4(2): 3-6

6. Paull, R. E. Soursop. In P. E. Shaw, H. T. Chan, Jr. and S. Nagy, (Eds.), Tropical and Subtropical Fruits. Auburndale, FL: Agscience. 1998: 386–400

7. Moghadamtousi SZ, Fadaeinasab M, Nikzad S, et al. Annona muricata (Annonaceae): A review of its traditional uses, isolated acetogenins and biological activities. Int J Mol Sci. 2015; 16(7): 15625-15658.

8. Meyer BN, Ferrigni NR, Putnam JE, et al. Brine shrimp: A convenient general bioassay for active plant constituents. Planta Med. 1982; 45(5): 31-34.

9. Taylor L Graviola. http://www.cancerplants.com/medicinal_plants/annona_m uricata.html Accessed February 1, 2014.

10. Rady I., Siddiqui I. A., Rady M., Mukhtar H. Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy. Cancer Letters. 2017; 402: 16–31. doi: 10.1016/ j.canlet.2017.05.010.

11. Frankish H. 15 million new cancer cases per year by 2020, says WHO. The Lancet. 2003; 361(9365): p. 1278. doi: 10.1016/S0140-6736(03)13038-3.

12. Siegel R. L., Miller K. D., Jemal A. Cancer statistics, 2018. CA: A Cancer Journal for Clinicians. 2018; 68(1): 7–30. doi: 10.3322/ caac.21442.

13. Moghadamtousi S., Fadaeinasab M., Nikzad S., Mohan G., Ali H., Kadir H. Annona muricata (Annonaceae): a review of its traditional uses, isolated acetogenins and biological activities. International Journal of Molecular Sciences. 2015; 16(7): 15625–15658. doi: 10.3390/ijms160715625.

14. Nussbaumer S., Bonnabry P., Veuthey J. L., Fleury-Souverain S. Analysis of anticancer drugs: a review. Talanta. 2011; 85(5): 2265–2289. doi: 10.1016/j.talanta.2011.08.034

15. Stan, S.D.; Singh, S.V.; Brand, R.E. Chemoprevention Strategies for Pancreatic Cancer. Nat. Rev. Gastroenterol. Hepatol. 2010; 7: 347–356.

16. Moghadamtousi, S.Z.; Kadir, H.A.; Paydar, M.; Rouhollahi, E.; Karimian, H. Annona muricata Leaves Induced Apoptosis in A549 Cells through Mitochondrial-Mediated Pathway and Involvement of NF-KB. BMC Complement. Altern. Med. 2014; 14: 299.

17. Zhao, G.X.; Rieser, M.J.; Hui, Y.H.; Miesbauer, L.R.; Smith, D.L.; McLaughlin, J.L. Biologically Active Acetogenins from Stem Bark of Asimina Triloba. Phytochemistry. 1993; 33: 1065–1073.

18. Kallifatidis, G.; Hoy, J.J.; Lokeshwar, B.L. Bioactive Natural Products for Chemoprevention and Treatment of Castration-Resistant Prostate Cancer. Semin. Cancer Biol. 2016; 40–41, 160–169.

19. Ko, E.Y.; Moon, A. Natural Products for Chemoprevention of Breast Cancer. J. Cancer Prev. 2015; 20: 223.

20. Hadisaputri, Y.E.; Habibah, U.; Abdullah, F.F.; Halimah, E.; Mutakin, M.; Megantara, S.; Abdulah, R.; Diantini, A. Antiproliferation Activity and Apoptotic Mechanism of Soursop (Annona muricata L.) Leaves Extract and Fractions on MCF7 Breast Cancer Cells. Breast Cancer Targets Ther. 2021; 13: 447.

21. Qazi, A.K.; Hussain, A.; Aga, M.A.; Ali, S.; Taneja, S.C.; Sharma, P.R.; Saxena, A.K.; Mondhe, D.M.; Hamid, A. Cell Specific Apoptosis by RLX Is Mediated by NFκB in Human Colon Carcinoma HCT-116 Cells. BMC Cell Biol. 2014; 15: 36.

22. Johnson, D.E.; Burtness, B.; Leemans, C.R.; Lui, V.W.Y.; Bauman, J.E.; Grandis, J.R. Head and Neck Squamous Cell Carcinoma. Nat. Rev. Dis. Primers. 2020; 6: 92.

23. Lucas, D.M.; Still, P.C.; Pérez, L.B.; Grever, M.R.; Kinghorn, A.D. Potential of Plant-Derived Natural Products in the Treatment of Leukemia and Lymphoma. Curr. Drug Targets. 2010; 11: 812.

24. Yang, H.; Liu, N.; Lee, S. Ethanol Extract of Annona muricata L Induces Liver Cancer Cell Apoptosis through ROS Pathway. Biomed. Pharmacol. J. 2016; 9: 919–925.

25. de Melo, J.G.; de Sousa Araújo, T.A.; de Almeida Castro, V.T.N.; de Vasconcelos Cabral, D.L.; do Desterro Rodrigues, M.; do Nascimento, S.C.; de Amorim, E.L.C.; de Albuquerque, U.P. Antiproliferative Activity, Antioxidant Capacity and Tannin Content in Plants of Semi-Arid Northeastern Brazil. Molecules. 2010; 15: 8534–8542.

26. Capes-Davis, A.; Theodosopoulos, G.; Atkin, I.; Drexler, H.G.; Kohara, A.; MacLeod, R.A.F.; Masters, J.R.; Nakamura, Y.; Reid, Y.A.; Reddel, R.R.; et al. Check Your Cultures! A List of Cross-Contaminated or Misidentified Cell Lines. Int. J. Cancer. 2010; 127: 1.

Received on 07.08.2024 Revised on 02.09.2024

Accepted on 20.09.2024 Published on 20.12.2024

Available online from November 25, 2024

Res. J. Pharmacognosy and Phytochem. 2024; 16(4):270-277.

DOI: 10.52711/0975-4385.2024.00050

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.