Annona Muricata (Soursop): The Natural Enemy of Cancer -A Comprehensive Review
Abstract
Annona muricata (commonly known as soursop or graviola) is a tropical plant widely recognized for its traditional medicinal applications and growing scientific interest, particularly for its anticancer potential. This review presents a comprehensive analysis of the phytochemical profile, pharmacological activities, and mechanisms underlying the anticancer effects of A. muricata. The plant is rich in annonaceous acetogenins, alkaloids, flavonoids, and phenolic compounds, with acetogenins such as annonacin and bullatacin demonstrating potent cytotoxicity against various cancer cell lines including breast, prostate, colon, pancreatic, and liver cancers. Mechanistically, these compounds induce apoptosis through mitochondrial dysfunction, arrest cell cycle progression, and inhibit key signaling pathways such as NF-κB and VEGF, effectively suppressing tumor growth and angiogenesis. Preclinical in vivo studies have confirmed tumor regression, enhanced antioxidant defense, and minimal systemic toxicity. However, concerns regarding annonacin-induced neurotoxicity and the lack of clinical trials limit its current therapeutic use. Innovative delivery systems, such as nanoformulations and lipid-based carriers, have shown promise in improving bioavailability and reducing toxicity. Despite the encouraging evidence, clinical validation remains absent, and standardized protocols for dosage, extract preparation, and safety are urgently needed. This review emphasizes the need for translational research to bridge the gap between traditional use and modern oncology. With rigorous scientific validation and regulatory oversight, Annona muricata holds the potential to emerge as a natural and effective anticancer agent.
Keywords:
Annona muricata, soursop, acetogenins, anticancer, apoptosis, nanoparticle delivery, natural products, cytotoxicity, phytochemicals, NF-κB inhibition
References
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5. Oberlies NH, Chang CJ, McLaughlin JL. Structure-activity relationships of diverse annonaceous acetogenins against human solid tumor cell lines. J Nat Prod. 1997;60(10):1004–9.
6. Yang C, Gundala SR, Mukkavilli R, Vangala S, Reid MD, Aneja R. Synergistic interactions among flavonoids from Annona muricata leaves in suppressing prostate cancer cell proliferation and migration. J Ethnopharmacol. 2015;194:1035–44.
7. Laurent D, Hoebeke J, Schwartz J. Soursop (Graviola) and atypical Parkinsonism: A case–control study. Neurology. 2006;66(9):1463–6.
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10. Pieme CA, Kumar SG, Dongmo MS, Moukette BM, Boyoum FF, Ngogang JY, et al. Antioxidant and anti-inflammatory activities of some traditional medicinal plants. J Ethnopharmacol. 2014;155(1):67–73.
11. Rady I, Bloch MB, Chamcheu RN, BanangMbeumi S, Anwar MR, Mohamed H, et al. Anticancer properties of graviola (Annona muricata): A comprehensive mechanistic review. Oxid Med Cell Longev. 2018;2018:1–21.
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13. Rachmaniah O, Rifa’i M. Cytotoxicity effect of soursop (Annona muricata L.) leaves ethanol extract on breast cancer cells (MCF-7). J Appl Pharm Sci. 2019;9(10):56–61.
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16. Osei-Asare C, Asare K, Agyapong G, Acheampong F, Boateng JO, Adinortey MB. Review on the ethnomedicinal uses, phytochemistry, and pharmacological properties of Annona muricata. Int J Drug Dev Res. 2020;12(3):1–11.
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18. Badrie N, Schauss AG. Soursop (Annona muricata L.): Composition, nutritional value, and therapeutic applications. Nutr Food Sci. 2010;40(3):217–26.
19. Jaramillo-Flores ME, González-Gallego G, Orozco-Villafuerte J, Paredes-López O. Bioactive compounds from Annona muricata: extraction, characterization, and biological activities. J Food Biochem. 2019;43(10):e12923.
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22. Ortiz-Ruiz A, Verde-Star MJ, Zaragoza-Arredondo C, Olivas-Aguirre M, Aguilar-Cruz C, Sánchez-Torres LE. Acetogenins in Annona muricata fruit pulp: Antioxidant activity and cytotoxic effect on human cancer cells. Molecules. 2021;26(18):5478.
23. Kim GS, Zeng L, Alali FQ, Rogers LL, Wu FE, McLaughlin JL. Bioactive annonaceous acetogenins: potent mitochondrial complex I inhibitors with diverse cytotoxicities. Bioorg Med Chem. 1998;6(3):312–20.
24. Zhang Y, Li Y, Wang Y, Tang Y, Wang Q, Zhang W. Inhibitory effect of graviola (Annona muricata) extract on pancreatic cancer cells through EGFR/ERK signaling pathway. Biomed Pharmacother. 2021;139:111647.
25. Baskar AA, Ignacimuthu S, Paulraj GM, Al Numair KS. Chemopreventive potential of Annona muricata against chemically induced hepatocellular carcinoma in rats. J Cancer Res Ther. 2012;8(3):387–93.
26. Torres MP, Rachagani S, Guha S, Johansson SL, Kumar S, Smith LM, et al. Graviola inhibits hypoxia-induced NADPH oxidase activity in pancreatic cancer cells: a potential mechanism for its anti-pancreatic cancer activity. Am J Transl Res. 2012;4(4):447–57.
27. Wu FE, Gu ZM, Zeng L, Zhao GX, Zhang Y, Schwedler JT, et al. Two new cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata. J Nat Prod. 1995;58(6):830–6.
28. Rupprecht JK, Hui YH, McLaughlin JL. Annonaceous acetogenins: a review. J Nat Prod. 1990;53(2):237–78.
29. Rachmani E, Retnoningrum DS, Estuningtyas A. Acetogenins isolated from Annona muricata induce apoptosis through mitochondrial pathway. Trop J Nat Prod Res. 2020;4(3):153–8.
30. Martínez-Aragón G, Suárez-Jiménez GM, Meléndez-Camargo ME, Delgado-Macuil R, Arévalo-Ruiz M, Domínguez-Ortiz MA. Cytotoxic effects of Annona muricata extracts in cervical cancer cell lines. Asian Pac J Cancer Prev. 2021;22(6):1921–6.
31. Nogueira JL, Corrêa RGC, Iwanaga CC, Dos Santos FV, Damasceno CA, De Lima TC. Toxicological studies of Annona muricata: a systematic review. J Ethnopharmacol. 2020;248:112344.
32. He M, Min J, Kong W, Wei X, Chen B, Peng X. The regulation of apoptosis by plant-derived polyphenols in human cancers. Oxid Med Cell Longev. 2019;2019:1–18.
33. Elvira-Torales LI, García-Alonso J, Periago MJ. Nutritional importance of carotenoids and their effect on liver health: A review. Antioxidants. 2019;8(7):229.
34. Rady I, Bloch MB, Chamcheu RN, BanangMbeumi S, Anwar MR, Mohamed H, et al. Molecular mechanisms of Annona muricata (Graviola) in cancer chemoprevention: A review. Curr Drug Targets. 2018;19(2):152–8.
35. Dong H, Chen Y, Zhang Y, Su M, Wu L, Pan X, et al. Natural products for cancer prevention: mechanisms of action and molecular targets. Front Pharmacol. 2021;12:669119.
36. Islam R, Hossen F, Hossain MA. Antimicrobial and cytotoxic activities of Annona muricata leaves extract. Int J Pharm Sci Res. 2013;4(8):3077–83.
37. Hernández J, Sáenz T, Fernández MA. Evaluation of the antinociceptive and anti-inflammatory effects of Annona muricata L. extracts. J Ethnopharmacol. 2007;111(3):490–5.
2. Moghadamtousi SZ, Abdul Kadir H, Hassandarvish P, Tajik H, Abubakar S, Zandi K. A review on antibacterial, antiviral, and antifungal activity of Annona muricata. Biomed Res Int. 2015;2015:118905.
3. Coria-Téllez AV, Montalvo-Gónzalez E, Yahia EM, Obledo-Vázquez EN. Annona muricata: A comprehensive review on its traditional medicinal uses, phytochemicals, pharmacological activities, mechanisms of action and toxicity. Arab J Chem. 2018;11(5):662–91.
4. Liaw CC, Chang FR, Lin CY, Chou CJ, Chiu HF, Wu MJ, et al. New cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata. J Nat Prod. 2002;65(4):470–5.
5. Oberlies NH, Chang CJ, McLaughlin JL. Structure-activity relationships of diverse annonaceous acetogenins against human solid tumor cell lines. J Nat Prod. 1997;60(10):1004–9.
6. Yang C, Gundala SR, Mukkavilli R, Vangala S, Reid MD, Aneja R. Synergistic interactions among flavonoids from Annona muricata leaves in suppressing prostate cancer cell proliferation and migration. J Ethnopharmacol. 2015;194:1035–44.
7. Laurent D, Hoebeke J, Schwartz J. Soursop (Graviola) and atypical Parkinsonism: A case–control study. Neurology. 2006;66(9):1463–6.
8. Moghadamtousi SZ, Fadaeinasab M, Nikzad S, Mohan G, Ali HM, Kadir HA. Annona muricata leaves: Biochemical constituents and functional properties. Evid Based Complement Alternat Med. 2015;2015:1–20.
9. George VC, Kumar DRN, Suresh PK, Kumar RA. Antioxidant, DNA protective efficacy and HPLC analysis of Annona muricata (soursop) extracts. J Food Sci Technol. 2015;52(4):2328–35.
10. Pieme CA, Kumar SG, Dongmo MS, Moukette BM, Boyoum FF, Ngogang JY, et al. Antioxidant and anti-inflammatory activities of some traditional medicinal plants. J Ethnopharmacol. 2014;155(1):67–73.
11. Rady I, Bloch MB, Chamcheu RN, BanangMbeumi S, Anwar MR, Mohamed H, et al. Anticancer properties of graviola (Annona muricata): A comprehensive mechanistic review. Oxid Med Cell Longev. 2018;2018:1–21.
12. Gavamukulya Y, Abou-Elella F, Wamunyokoli F, El-Shemy HA. Phytochemical screening, anti-oxidant activity and in vitro anti-cancer potential of ethanolic leaf extract of Annona muricata. Asian Pac J Trop Med. 2014;7(Suppl 1):S355–63.
13. Rachmaniah O, Rifa’i M. Cytotoxicity effect of soursop (Annona muricata L.) leaves ethanol extract on breast cancer cells (MCF-7). J Appl Pharm Sci. 2019;9(10):56–61.
14. Pandey A, Ramasamy K, Abdul Majeed AB, Abdullah N, Murugaiyah V. In vitro and in vivo anticancer effects of Annona muricata leaf extract on chemically induced hepatocellular carcinoma in rats. J Ethnopharmacol. 2021;266:113420.
15. Rachmani E, Retnoningrum DS, Estuningtyas A. Apoptosis induction of cancer cells via mitochondrial pathways by annonacin isolated from Annona muricata. Trop J Nat Prod Res. 2020;4(3):154–60.
16. Osei-Asare C, Asare K, Agyapong G, Acheampong F, Boateng JO, Adinortey MB. Review on the ethnomedicinal uses, phytochemistry, and pharmacological properties of Annona muricata. Int J Drug Dev Res. 2020;12(3):1–11.
17. Dawidowicz AL, Wianowska D, Baraniak B. The antioxidant properties of alcoholic extracts from herbs and their seasonal variation. J Food Chem. 2006;100(3):940–5.
18. Badrie N, Schauss AG. Soursop (Annona muricata L.): Composition, nutritional value, and therapeutic applications. Nutr Food Sci. 2010;40(3):217–26.
19. Jaramillo-Flores ME, González-Gallego G, Orozco-Villafuerte J, Paredes-López O. Bioactive compounds from Annona muricata: extraction, characterization, and biological activities. J Food Biochem. 2019;43(10):e12923.
20. Paredes-López O, Cervantes-Ceja ML, Vigna-Pérez M, Hernández-Pérez T. Berries: improving human health and healthy aging, and promoting quality life—a review. Plant Foods Hum Nutr. 2010;65(3):299–308.
21. Gavamukulya Y, Wamunyokoli F, El-Shemy HA. Comparative phytochemical composition, antioxidant and anticancer activities of leaf and root extracts of Annona muricata. J Med Plants Res. 2015;9(43):1100–8.
22. Ortiz-Ruiz A, Verde-Star MJ, Zaragoza-Arredondo C, Olivas-Aguirre M, Aguilar-Cruz C, Sánchez-Torres LE. Acetogenins in Annona muricata fruit pulp: Antioxidant activity and cytotoxic effect on human cancer cells. Molecules. 2021;26(18):5478.
23. Kim GS, Zeng L, Alali FQ, Rogers LL, Wu FE, McLaughlin JL. Bioactive annonaceous acetogenins: potent mitochondrial complex I inhibitors with diverse cytotoxicities. Bioorg Med Chem. 1998;6(3):312–20.
24. Zhang Y, Li Y, Wang Y, Tang Y, Wang Q, Zhang W. Inhibitory effect of graviola (Annona muricata) extract on pancreatic cancer cells through EGFR/ERK signaling pathway. Biomed Pharmacother. 2021;139:111647.
25. Baskar AA, Ignacimuthu S, Paulraj GM, Al Numair KS. Chemopreventive potential of Annona muricata against chemically induced hepatocellular carcinoma in rats. J Cancer Res Ther. 2012;8(3):387–93.
26. Torres MP, Rachagani S, Guha S, Johansson SL, Kumar S, Smith LM, et al. Graviola inhibits hypoxia-induced NADPH oxidase activity in pancreatic cancer cells: a potential mechanism for its anti-pancreatic cancer activity. Am J Transl Res. 2012;4(4):447–57.
27. Wu FE, Gu ZM, Zeng L, Zhao GX, Zhang Y, Schwedler JT, et al. Two new cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata. J Nat Prod. 1995;58(6):830–6.
28. Rupprecht JK, Hui YH, McLaughlin JL. Annonaceous acetogenins: a review. J Nat Prod. 1990;53(2):237–78.
29. Rachmani E, Retnoningrum DS, Estuningtyas A. Acetogenins isolated from Annona muricata induce apoptosis through mitochondrial pathway. Trop J Nat Prod Res. 2020;4(3):153–8.
30. Martínez-Aragón G, Suárez-Jiménez GM, Meléndez-Camargo ME, Delgado-Macuil R, Arévalo-Ruiz M, Domínguez-Ortiz MA. Cytotoxic effects of Annona muricata extracts in cervical cancer cell lines. Asian Pac J Cancer Prev. 2021;22(6):1921–6.
31. Nogueira JL, Corrêa RGC, Iwanaga CC, Dos Santos FV, Damasceno CA, De Lima TC. Toxicological studies of Annona muricata: a systematic review. J Ethnopharmacol. 2020;248:112344.
32. He M, Min J, Kong W, Wei X, Chen B, Peng X. The regulation of apoptosis by plant-derived polyphenols in human cancers. Oxid Med Cell Longev. 2019;2019:1–18.
33. Elvira-Torales LI, García-Alonso J, Periago MJ. Nutritional importance of carotenoids and their effect on liver health: A review. Antioxidants. 2019;8(7):229.
34. Rady I, Bloch MB, Chamcheu RN, BanangMbeumi S, Anwar MR, Mohamed H, et al. Molecular mechanisms of Annona muricata (Graviola) in cancer chemoprevention: A review. Curr Drug Targets. 2018;19(2):152–8.
35. Dong H, Chen Y, Zhang Y, Su M, Wu L, Pan X, et al. Natural products for cancer prevention: mechanisms of action and molecular targets. Front Pharmacol. 2021;12:669119.
36. Islam R, Hossen F, Hossain MA. Antimicrobial and cytotoxic activities of Annona muricata leaves extract. Int J Pharm Sci Res. 2013;4(8):3077–83.
37. Hernández J, Sáenz T, Fernández MA. Evaluation of the antinociceptive and anti-inflammatory effects of Annona muricata L. extracts. J Ethnopharmacol. 2007;111(3):490–5.
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Bhimavarapu, B. T., Patibandla, J., & A, S. (2025). Annona Muricata (Soursop): The Natural Enemy of Cancer -A Comprehensive Review. Journal of Integral Sciences, 8(3), 10-15. https://doi.org/10.37022/jis.v8i3.110
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