Study of the Anticancer Activity of Annona squamosa Seeds
Anticancer Activity for Annona seeds
DOI:
https://doi.org/10.29409/xqq6c722Keywords:
Annona seeds, Anticancer activity, MCF-7 cell line, MDA cell line, REF cellsAbstract
The whole world is still searching for natural sources in various fields, especially natural alternatives for treating diseases and various health disorders, most notably in the treatment of tumors and cancers. The current study included an in vitro anticancer estimation of Annona seed extract on two cell lines of breast cancer (MCF-7& MDA-231) and one normal cell line represented by REF. Active constituents in the seeds were extracted by maceration with 70% ethanol. General phytochemical tests were conducted to investigate the active constituents of the extracted seeds. The phenolic compounds and flavonoids in the extracted residue were estimated via HPLC in addition to the nonpolar substances in the seed residue. The three cell lines (MCF-7, MDA-231 & REF) were subjected to different concentrations of seed extract for the anticancer assay. Results showed that the ethanolic extract residue was 8.4 g from 90 g of powdered plant seeds, representing 9.34% W/W, and the seed residue contained many active constituents. The HPLC results indicated that the seed extract was rich in gallic acid, caffeic acid, pyrogaloll, cinnamic acid, p-coumaric acid and, to a lesser extent, chlorogenic acid, which are simple phenolic compounds. Luteolin, kaempferol, and apegnine and lower amounts of quercetin, rutin and catechin, which are flavonoids, were also detected in the residue extracted from the seeds. For the nonpolar seeds, the following components were detected at a decreasing level: β-myrcene, p-cymene, α-pinene, eugenol, and β-pinene. The anticancer activity of the seed extract at several concentrations differed across the three types of cell lines in the present study.
Author Declarations:
Acknowledgment
The authors are grateful to researchers at the Biotechnology Research Center, University of Al-Nahrain, for their scientific support.
Conflicts of interest
There are no conflicts of interest regarding the publication of this manuscript.
Funding
The research did not receive any financial support from any institution.
Author Contribution
All the authors confirm their contributions to the paper, including the study conception; the study design; and the data collection, analysis, and interpretation of the results. All the authors reviewed the results and approved the final version of the manuscript.
Data availablility statement
The corresponding author will provide the data upon reasonable request.
References
Xiang, L. Review on Annona squamosa L.: Phytochemicals and Biological Activities.The American Journal of Chinese Medicine, 2017,Vol. 45, No. 5, 1–32
Gavamukulya, Y. ; Wamunyokoli, F. and El-Shemy, H. A. “Annona muricata: Is the natural therapy to most disease conditions including cancer growing in our backyard? A systematic review of its research history and future prospects,” Asian Pacific Journal of Tropical Medicine, 2017,vol. 10, no. 9, pp. 835-848. DOI: https://doi.org/10.1016/j.apjtm.2017.08.009
Ivone, L.S. ; Antonio, M. ; Edna, R. A. and Luiza, H. M. Soursop (Annona muricata) Properties and Perspectives for Integral Valorization. Foods 2023, 12, 1448. https://doi.org/10.3390/foods12071448 DOI: https://doi.org/10.3390/foods12071448
Siti, N. Z. ; Hidayah, M. N. ; Mohd, S. A. K.; Taha, A. Q. ; Syahida, M. ; Adlin, A.; Norazlan, M.M.; Hamizah, S.H.; Syarul, N.B.and Ahmed, M. Annona muricata: Comprehensive Review on theEthnomedicinal, Phytochemistry, and Pharmacological AspectsFocusing on Antidiabetic Properties. Life 2023, 13, 353. https://doi.org/10.3390/life13020353. DOI: https://doi.org/10.3390/life13020353
Uğurbaş, M. V.; Ogurčáková, D.; Haus, M.; Boroňová, I.; Čuchráč. L. and Vašková, J. “Effect of Annona Muricata Aqueous Leaf Extract on Reactive Oxygen and Nitrogen Species.,” European Review for Medical and Pharmacological Sciences, 2022, vol. 26, no. 18, pp. 6497-6504.
Nugraha, A.S.; Damayanti, Y.D.; Wangchuk, P.; Keller, P.A. Anti-Infective and anti-Cancer properties of the Annona Species: Their ethnomedicinal uses, alkaloid diversity, and pharmacological activities. Molecules.2019, 24, 4419. DOI: https://doi.org/10.3390/molecules24234419
Al Kazman, B.S.M.; Harnett,J.E.; Hanrahan, J.R. Traditional Uses,Phytochemistry and PharmacologicalActivities of Annonacae. Molecules. 2022, 27, 3462. https://www.researchgate.net/publication/360944027. DOI: https://doi.org/10.3390/molecules27113462
Sampada S. S.; Satish Y. G. and Kamalinder, K. S. In Vitro Effect on Plasmodium falciparum and Plasmodium berghei of Annomaal, an Oily Fraction Obtained from the Seeds of Annona squamosa. Molecules. 2023 Jul; 28(14): 5472. 10.3390/molecules28145472 PMCID: PMC10383673 DOI: https://doi.org/10.3390/molecules28145472
Amala DevA.R, Sonia Mol Joseph Anticancer potential of Annona genus: A detailed review. Journal of the Indian Chemical Society (2021), 98; 100231. DOI: https://doi.org/10.1016/j.jics.2021.100231
Chang, X.; Zhang, T.; Zhang, W.; Zhao, Z.; Sun, J. Natural Drugs as a Treatment Strategy for Cardiovascular Disease through the Regulation of Oxidative Stress. Oxidative Med. Cell. Longev. 2020, 5430407. DOI: https://doi.org/10.1155/2020/5430407
Vagula, J.M.; Visentainer, J.V.; Lopes, A.P.; Maistrovicz, F.C.; Rotta, E.M.; Suzuki, R.M. Antioxidant activity of fifteen seeds from fruit processing residues by different methods. Acta Scientiarum. Technology, 2019, 41, e35043. DOI: https://doi.org/10.4025/actascitechnol.v41i2.35043
Ruddaraju LK, Vijaykumar PPN, Pammi SVN, Swamy PV, Murthy KVR. Synergetic antibacterial and anticarcinogenic effects of Annona squamosa leaf extract. fapjcp.2019.20.9.2831.https://doi.org/10.1016/j.mssp.2019.05.007. 10.31557/2 DOI: https://doi.org/10.1016/j.mssp.2019.05.007
Lim, H.-S.; Kim, Y.J.; Sohn, E.; Yoon, J.; Kim, B.-Y.; Jeong, S.-J. Annona atemoya leaf extract ameliorates cognitive impairment in amyloid-_ injected Alzheimer’s disease-like mouse model. Exp. Biol. Med. 2019,32;2,67-72.
Sohn, E.; Lim, H.-S.; Kim, Y.J.; Kim, B.-Y.; Jeong, S.-J. Annona atemoya Leaf Extract Improves Scopolamine-Induced Memory Impairment by Preventing Hippocampal Cholinergic Dysfunction and Neuronal Cell Death. Int. J. Mol. Sci. 2019, 20, 3538. DOI: https://doi.org/10.3390/ijms20143538
Ma, C.; Chen, Y.; Chen, J.; Li, X.; Chen, Y. A Review on Annona squamosa L.: Phytochemicals and Biological Activities. Am. J. Chin. Med. 2017, 45, 933–964. DOI: https://doi.org/10.1142/S0192415X17500501
Zhu, H.; Chen, L.; Yu, J.; Cui, L.; Ali, I.; Song, X.;Wang, X. Flavonoid epimers from custard apple leaves, a rapid screening and separation by HSCCC and their antioxidant and hypoglycaemic activities evaluation. Sci. Rep. 2020, 10, 8819. DOI: https://doi.org/10.1038/s41598-020-65769-5
Kumar, M., Changan, S., Tomar, M., Prajapati, U., Saurabh, V., Hasan, M., Sasi, M., Maheshwari, C., Singh, S., Dhumal, S., Radha., Thakur, M., Punia, S., Satankar, V., Amarowicz, R. And Mekhemar, M.. Custard apple (Annona squamosa L.) leaves: nutritional composition, phytochemical profile, and health-promoting biological activities. Biomolecules , 2021, vol. 11, no. 5, pp. 614. DOI: https://doi.org/10.3390/biom11050614
Othman, L., Sleiman, A. and Abdel-Massih, R.M.,. Antimicrobial Activity of Polyphenols and Alkaloids in Middle Eastern Plants. Frontiers in Microbiology, 2019, vol. 10, pp. 911. http:// dx.doi.org/10.3389/fmicb.2019.00911. PMid:31156565. DOI: https://doi.org/10.3389/fmicb.2019.00911
Mannino, G.; Gentile, C.; Porcu, A.; Agliassa, C.; Caradonna, F.; Bertea, C.M. Chemical Profile and Biological Activity of Cherimoya (Annona cherimola Mill.) and Atemoya (Annona atemoya) Leaves. Molecules 2020, 25, 2612. DOI: https://doi.org/10.3390/molecules25112612
Mohamed G. S.; Marwa M. A; Nourhan M. A.& Sobhy A. El‑S.. Nutritional, phytochemical, and in vitro anticancer potential of sugar apple (Annona squamosa) fruits. Scientific Reports | (2021) 11:6224 | https://doi.org/10.1038/s41598-021-85772-8 DOI: https://doi.org/10.1038/s41598-021-85772-8
Siti Mariam Abdul Wahab, Ibrahim J.; Md, A. H. and Laiba, A. Exploring the Leaves of Annona muricata L. as a Source of Potential Anti-inflammatory and Anticancer Agents. Frontiers in Pharmacology | www.frontiersin.org 1 June 2018 | Volume 9:661. doi: 10.3389/fphar.2018.00661 DOI: https://doi.org/10.3389/fphar.2018.00661
Olas, B. The Antioxidant Potential of Graviola and Its Potential Medicinal Application. Nutrients 2023, 15, 402. [CrossRef] DOI: https://doi.org/10.3390/nu15020402
Veerakumar S, Amanulla SSD, Ramanathan K. Anti-cancer efficacy of ethanolic extracts from various parts of Annona squamosa on MCF-7 cell line. J. Pharmacogn. Phytotherapy 2016;8:147–54. https://doi.org/10.5897/jpp2016.0398. DOI: https://doi.org/10.5897/JPP2016.0398
Alaqeela, N. K.; Almalkib, W. H. ; Binothmanc, N. ; Aljadanic, M.; Al-Dhuayana, I. S. ; Alnamshana, M. M. ; Almulhimd, J. ; Alqosaibia, A. I. ; Ajmale, M. R.; Alammarif, D. M. and Tariqueg, M. The inhibitory and anticancer properties of Annona squamosa L. seed extracts.Brazilian Journal of Biology, 2022, vol. 82, e268250 Article in Brazilian Journal of Biology · January 2022B DOI: https://doi.org/10.1590/1519-6984.268250
Vikas B, Anil S, Remani P. Cytotoxicity profiling of Annona squamosa in cancer cell lines. Asian Pac. J. Cancer Prev. APJCP 2019;20:2831–40. https://doi.org/ DOI: https://doi.org/10.31557/APJCP.2019.20.9.2831
Haykal T, Nasr P, Hodroj MH, Taleb RI, Sarkis R, Moujabber MNE, Rizk S. Annona cherimola seed extract activates extrinsic and intrinsic apoptotic pathways in leukemic cells. Toxins 2019;11:506. https://doi.org/10.3390/toxins11090506. DOI: https://doi.org/10.3390/toxins11090506
Son, Y.; Lee, H.; Son, S.Y.; Lee, C.H.; Kim, S.Y.; Lim, Y. Ameliorative Effect of Annona muricata (Graviola) Extract on Hyperglycemia Induced Hepatic Damage in Type 2 Diabetic Mice. Antioxidants 2021, 10, 1546. DOI: https://doi.org/10.3390/antiox10101546
Al Yaad, K.M.; Elsaid, S.F.G.; Abdraboh, M.E.; Al-Doaiss, A.A. Effect of Graviola (Annona Muricata l.) and Ginger (Zingiber Officinale Roscoe) on Diabetes Mellitus Induced in Male Wistar Albino Rats. Folia. Biol. 2019, 65, 275–284. DOI: https://doi.org/10.14712/fb2019065050275
Sasso, S.; Sampaio, E.; Souza, P.C.; Santana, L.F.; Cardoso, C.A.L.; Alves, F.M.; Portugal, L.C.; Faria, B.B.; Silva, A.F.; Motta-Castro, A.R.; et al. Use of an Extract of Annona muricata Linn to Prevent High-Fat Diet Induced Metabolic Disorders in C57BL/6 Mice. Nutrients 2019, 11, 1509. DOI: https://doi.org/10.3390/nu11071509
Hu, T.; Lu, X.Y.; Shi, J.J.; Liu, X.Q.; Chen, Q.B.;Wang, Q.; Chen, Y.B.; Zhang, S.J. Quercetin protects against diabetic encephalopathy via SIRT1/NLRP3 pathway in db/db mice. J. Cell. Mol. Med. 2020, 24, 3449–3459. DOI: https://doi.org/10.1111/jcmm.15026
Heaji L.; Sun Y. K. and Yunsook L. Annona muricate Extract Supplementation Contributes to Improve Aberrant Multi-Organ Energy Metabolism via Muscle–Brain Connectivity in Diabetic Mice. Nutrients 2023, 15, 2559. https://doi.org/10.3390/nu15112559 DOI: https://doi.org/10.3390/nu15112559
Ma C.Y.; Lu J.H.; Xiang L. X.; Liu X.;Chen J.W. Eight new cytotoxic annonaceous acetogenins from the seeds of Annona squamosa. Chin. J. Nat. Med. 2019;17: 291–7. https://doi.org/10.1016/s1875-5364(19)30032-9. DOI: https://doi.org/10.1016/S1875-5364(19)30032-9
Coria-T.A.; Montalvo-G. E.; Yahia E.; Obledo-V.E. Annona muricata: a comprehensive review on its traditional medicinal uses, phytochemicals, pharmacological activities,mechanisms of action and toxicity. Arab J Chem 2016; http://dx.doi.org/10.1016/j.arabjc.2016.01.004. DOI: https://doi.org/10.1016/j.arabjc.2016.01.004
Camilo D. G.; Juan M.G.G.; Joao V. D.; Young H.C.; Damaris S. and Omar E. A New Lignan from Annona squamosa L. (Annonaceae) Demonstrates Vasorelaxant Effects In Vitro. Molecules 2023, 28, 4256. https://doi.org/10.3390/molecules28114256 DOI: https://doi.org/10.3390/molecules28114256
Win M. and Myat M. K. Pharmacological Activities of Annona squamosa: UpdatedReview. International Journal of Pharmacy and Chemistry2017; 3(6): 86-93http://www.sciencepublishinggroup.com/j/ijpcdoi: 10.11648/j.ijpc.20170306.14 DOI: https://doi.org/10.11648/j.ijpc.20170306.14
Shaima R.I.; Enas S. A.; Zainab F. M.; Hazim I. A. Study the Effects of Annona sp. Extract on Some Physiological Parameters and Fertility in Diabetic Mice. Iraqi Journal of Science, 2024, Vol. 65, No. 6, pp: 3027-3039 DOI: https://doi.org/10.24996/ijs.2024.65.6.6
Alsenosy, A.A.; El-Far, A.H.; Sadek, K.M.; Ibrahim, S.A.; Atta, M.S.; Sayed-Ahmed, A.; Al Jaouni, S.K.; Mousa, S.A. Graviola (Annona muricata) attenuates behavioural alterations and testicular oxidative stress induced by streptozotocin in diabetic rats. PLoS ONE 2019, 14, e0222410. DOI: https://doi.org/10.1371/journal.pone.0222410
Harborne,J. phytochemical methods, A guide to modern techniquos of plant analysis . (1984);Second edition , chapman and Hall , London: 169-172.
Richird, I. Natural products Isolation. Second edition (2000); New York.
Asif,M.; Mkapiand, G. and Khodadadi, E. .Medicinal uses and chemistry of flavonoid contents of some common edible tropical plants Journal of Paramedical Sciences (JPS), (2013);4(3):45-56.
Holliday, D. L. and Speirs, V. . Choosing the right cell line for breast cancer research. Breast cancer research, 2011, 13(4), 215. DOI: https://doi.org/10.1186/bcr2889
Lee, A. V.; et al. “MCF-7 Cells—Changing the Course of Breast Cancer Research and Care for 45 Years”. Journal of the National Cancer Institute. (1 July 2015). 107 (7): djv073. DOI: https://doi.org/10.1093/jnci/djv073
Soule, H. D; Vazquez J; Long A; Albert S; Brennan M. “A human cell line from a pleural effusion derived from a breast carcinoma”. Journal of the National Cancer Institute. (1973). , 51 (5): 1409 -1416. DOI: https://doi.org/10.1093/jnci/51.5.1409
Freshney,I. Culture of Animal Cells .A manual basic technique 4th edition, 2000, Wiley-Liss.Pp166.
Sabrina, B.; Benmekhebib, L.; Boubekria, N.; Rebbas ,K..; Brouardd, I.; Djamila, Z.; Benayachea, S. and Benayach, F. Antibacterial And Antioxidant Potential Of Lepidium draba L. (Brascicaceae). Research Journal of Pharmaceutical, Biological and Chemical Sciences Compositional Study, (2016);7(2):283-287.
Statistical Analysis System, SAS.User’s Guide. Statistical. Version 9.6th ed. SAS. Inst. Inc. Cary. N.C. USA. 2018
(Bader O. Almutairi, Ahmed Sholiah Mater, Mikhlid H. Almutairi. In vitro antiproliferative efficacy of Annona muricata seed and fruit extracts on several cancer cell lines. DE GRUYTEROpen Chemistry 2023; 21: 20220350. DOI: https://doi.org/10.1515/chem-2022-0350
Ajlal A. A. , Mukhtar R. H., Muftah A. S., and Fairouz A. Phyto-pharmaceuticals and biological study on graviola (Annona muricata L.) fruit and dietary supplement of graviola sold on the Libyan market as a cancer cure against TCA induce hepatotoxicity in mice. Cancer Biology 2018;8(2) http://www.cancerbio.net
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