Inhibition of MCF-7 Cancer Cells by Ethanol Extract of Soursop (Annona muricata L.) and Johar (Senna siamea L) Leaves In Vitro and In Silico as Anti-Breast Cancer
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Abstract
Soursop (Annona muricata L.) is a plant with relatively high antioxidant properties due to its polar active compounds. Several studies have also reported the presence of these polar compounds in johar leaves (Senna siamea L.), leading to their use as an effective anticancer remedy. Therefore, this study aims to determine the inhibitory activity of the ethanol extract of soursop and johar leaves and their combination against MCF-7 cancer cells. The combination of ethanol extract of soursop and johar leaves was made with a ratio of soursop leaves (AM): johar leaves (SS) of 1:1, 1:3, and 3:1. Anticancer inhibition in test samples was carried out using a toxicity and cytotoxicity approach, as well as determining the selectivity index value using the MTT method. The toxicity value was then determined using the BSLT method, with doxorubicin as the positive control. Molecular docking of the active compounds of the extract was carried out in silico. The results showed that the cytotoxicity of the combination of soursop and johar leaves 3:1 had an IC50 value of 89.82 ppm against MCF-7 cells and 209.22 ppm against NIH-3T3 cells. The toxicity and selectivity index values of the 3:1 combination were 67.76 ppm and 2.32, respectively. The active compounds rhein, chrysophanol, and luteolin had the best docking as anticancer agents during molecular docking. Based on these results, soursop and johar leaves extract and their combination had inhibitory activity on breast cancer cells, with the best activity being the AM:SS (3:1) extract.
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1.WHO. Breast cancer. World Health Organization. [Online]. 2023 [cited 2023 Dec 10]. Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer
2.Zhu JW, Charkhchi P, Adekunte S, Akbari MR. What Is Known about Breast Cancer in Young Women?. Cancers (Basel). 2023; 15(6):1917.
3.Strasser A, Vaux DL. Cell Death in the Origin and Treatment of Cancer. Mol Cell. 2020; 78(6):1045-1054.
4.Catalano A, Iacopetta D, Ceramella J, Scumaci D, Giuzio F, Saturnino C, Aquaro S, Rosano C, Sinicropi MS. Multidrug Resistance (MDR): A Widespread Phenomenon in Pharmacological Therapies. Molecules. 2022; 27(3):616.
5.Kim SD, Kwag EB, Yang MX, Yoo HS. Efficacy and Safety of Ginger on the Side Effects of Chemotherapy in Breast Cancer Patients: Systematic Review and Meta-Analysis. Int J Mol Sci. 2022 ;23(19): 11267.
6.Gavamukulya Y, Abou-Elella F, Wamunyokoli F, AEl-Shemy H. Phytochemical screening, antioxidant activity and in vitro anticancer potential of ethanolic and water leaves extracts of Annona muricata (Graviola). Asian Pac J Trop Med. 2014; 7S1:S355-S363.
7.Nguyen MT, Nguyen VT, Minh LV, Trieu LH, Cang MH, Bui LB, Le XT, Danh VT. Determination of the phytochemical screening, total polyphenols, flavonoids content, and antioxidant activity of soursop leaves (Annona muricata Linn.). IOP Conf Ser Mater Sci Eng. 2020; 736(6):62011.
8.Ilango S, Sahoo DK, Paital B, Kathirvel K, Gabriel JI, Subramaniam K, Jayachandran P, Dash RK, Hati AK, Behera TR, Mishra P, Nirmaladevi RA. A Review on Annona muricata and Its Anticancer Activity. Cancers (Basel). 2022; 14(18):4539.
9.Engel N, Falodun A, Kühn J, Kragl U, Langer P, Nebe B. Pro-apoptotic and anti-adhesive effects of four African plant extracts on the breast cancer cell line MCF-7. BMC Complement Altern Med. 2014; 14:334.
10.Brentnall M, Rodriguez-Menocal L, De Guevara RL, Cepero E, Boise LH. Caspase-9, caspase-3, and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol. 2013; 14:32.
11.Hadisaputri YE, Habibah U, Abdullah FF, 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 (Dove Med Press. 2021; 13:447-457.
12.Nwonuma CO, Balogun EA, Gyebi GA. Evaluation of Antimalarial Activity of Ethanolic Extract of Annona muricata L.: An in vivo and an in silico Approach. J Evidence-Based Integr Med. 2023; 28:1-30.
13.Agbodjogbe WKDD, Tito ASI, Adjakpahoun G, Messan F, Dansou PH. Antioxidant properties of Senna siamea and effects on sports performance in Wistar rats. Int J Biol Chem Sci. 2022;16(3):1193-1203.
14.Hassan IA, Nasiru IA, Malut AM, Ibrahim Abdulkadir S, Ali AS. Phytochemical studies and thin layer chromatography of leaves and flower extracts of Senna siamea Lam for possible biomedical applications. J Pharmacogn Phyther. 2015; 7(3):18-26.
15.Momin MAM, Bellah SF, Afrose A, Urmi KF, Hamid K, Rana MS. Phytochemical screening and cytotoxicity potential of ethanolic extracts of Senna siamea leaves. J Pharm Sci Res. 2012;4(8):1877-1879.
16.Gebrehiwot H, Ensermu U, Dekebo A, Endale M, Hunsen M. Exploring the medicinal potential of Senna siamea roots: an integrated study of antibacterial and antioxidant activities, phytochemical analysis, ADMET profiling, and molecular docking insights. Appl Biol Chem. 2024;67(48):1-22.
17.Asbin Mary X, Syed Ali M, Anuradha V, Yogananth N, Vardhana J, Vinoth Kumar P. Induction of Apoptosis by Methanolic Extract of Rhizophora mucronata Lam on MCF-7 Cell Line. Res J Pharm Technol. 2022; 15(11):5021-5025.
18.Comşa Ş, Cîmpean AM, Raica M. The story of MCF-7 breast cancer cell line: 40 Years of experience in research. Anticancer Res. 2015; 35(6):3147-3154.
19.Chunarkar-Patil P, Kaleem M, Mishra R, Ray S, Ahmad A, Verma D, Bhayye S, Dubey R, Singh HN, Kumar S. Anticancer Drug Discovery Based on Natural Products: From Computational Approaches to Clinical Studies. Biomedicines. 2024;12(1):201.
20.Indrayanto G, Putra GS, Suhud F. Chapter Six - Validation of in vitro bioassay methods: Application in herbal drug research. In: Al-Majed Excipients and Related Methodology AABTP of DS, ed. Vol 46. Academic Press; 2021:273-307.
21.Rahimi AM, Cai M, Hoyer-Fender S. Heterogeneity of the NIH3T3 Fibroblast Cell Line. Cells. 2022; 11(17):2677.
22.Ray A. Cancer preventive role of selected dietary factors. Indian J Cancer. 2005;42(1):15-24.
23.Priatna PA, Pratama RR, Widyowati R, Sukardiman. Molecular Docking Estrogen Receptor Alpha Antagonist and P53-MDM2 Inhibitor, ADMET Prediction of Alkaloid Compound from Mitragyna speciosa for Breast Cancer Therapy. Pharmacogn J. 2022; 14(6):912-916
24.Ho TX, Nguyen TN, Tran HTT, Nguyen TT, Guerrae IR, Doan PL, Tran TD. In Silico Prediction of Anti-Inflammatory Potential of Isolated Compounds from Enhalus acoroides. Trop J Nat Prod Res. 2025; 9(2):439-446.
25.Muhammed MT, Esin AY. Molecular Docking: Principles, Advances, and Its Applications in Drug Discovery. Lett Drug Des Discov. 2024; 21(3):480-495.
26.Patil, Vishwajit S, Patil PA. Molecular Docking: A useful approach of Drug Discovery on the Basis of their Structure. Asian J Pharm Res. 2023; 13(3):191-195.
27.Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010; 31(2):455-461.
28.Rutuja PP, Sachin HR. Role of Autodock Vina in PyRx Molecular Docking. Asian J Res Chem. 2021; 14(2):132-134.
29.Nagalakshmi V, Lavanya J, Bhavya B, Riya V, Venugopal B, Sai Ramesh A. In-silico Profiling of Deleterious Non-Synonymous SNPs of Homogentisate 1, 2 Dioxygenase (HGD) Gene for Early Diagnosis of "Alkaptonuria." Res J Pharm Technol. 2022; 15(9):3898-3904.
30.Selvadurai S, Shanmugapandiyan P. Preliminary Phytochemical Analysis on The Leaves Extracts of Sida acuta Burm.f. and Sida rhombifolia Linn. Family Malvaceae. Res J Pharm Technol. 2022; 15(4):1512-1516.
31.Rasyid SA, Bintang M, As’ad S, Miskad U, Minhajat R, Surya RA. Qualitative Phytochemical Screening and Effectiveness Analysis of Batissa violacea celebensis Martens 1897 Crude extract against Antioxidant and Cytotoxic Activity. Res J Pharm Technol. 2022; 15(1):263-269.
32.Noviardi H, Iswantini D, Mulijani S, Wahyudi ST, Khusniati T, Sulistiani S. Anti-inflammatory activity of the metabolite extract of Lactobacillus plantarum Su-ls29 on lipopolysaccharide-induced RAW 264.7 macrophage cells. J Appl Pharm Sci. 2023; 14(01):148-158.
33.Senthilraja P, Kathiresan K. In vitro cytotoxicity MTT assay in Vero, HepG2, and MCF-7 cell lines study of marine yeast. J Appl Pharm Sci. 2015; 5(3):80-84.
34.Ali A, Malipatil M, Ahmed L. MTT Assay on Anticancer properties of the different extracts of roots of Lantana camara Linn. Res J Pharm Technol. 2024; 17(3):1166-2.
35.Sudhakar P, Pushkalai SP, Sabarinath C, Priyadharshini S, Haripriya S. Molecular docking and synthesis of 1, 2, 4 triazin analogue of diclofenac as a potential ligand for parkinson's. Res J Pharmacol Pharmacodyn. 2018; 10(1):8.
36.Meena DK, Sahoo AK, Swain HS, Borah S, -Srivastava PP, Sahu NP, Das BK. Prospects and perspectives of virtual in-vitro toxicity studies on herbal extracts of Terminalia arjuna with enhanced stratagem in Artemia salina model: A panacea to explicit the credence of solvent system in brine shrimp lethality bioassay. Emirates J Food Agric. 2020; 32(1):25-37.
37.Clarkson C, Maharaj VJ, Crouch NR, Grace OM, Pillay P, Matsabisa MG, Bhagwandin N, Smith PJ, Folb PI. In vitro antiplasmodial activity of medicinal plants native to or naturalised in South Africa. J Ethnopharmacol. 2004; 92(2-3):177-191.
38.Taylor P, Colman L, Bajoon J. The search for plants with anticancer activity: Pitfalls at the early stages. J Ethnopharmacol. 2014; 158:246-254.
39.Fithrotunnisa Q, Arsianti A, Kurniawan G, Qorina F, Tejaputri NA, Azizah NN. In vitro cytotoxicity of Hibiscus sabdariffa Linn extracts on A549 lung cancer cell line. Pharmacogn J. 2020; 12(1):14-19.
40.Atjanasuppat K, Wongkham W, Meepowpan P, Kittakoop P, Sobhon P, Bartlett A, Whitfield PJ. In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand. J Ethnopharmacol. 2009; 123(3):475-482.
41.Kciuk M, Gielecińska A, Mujwar S, Kołat D, Kałuzińska-Kołat Ż, Celik I, Kontek R. Doxorubicin-An Agent with Multiple Mechanisms of Anticancer Activity. Cells. 2023; 12(4):659.
42.Pritchett JC, Naesens L, Montoya J. Treating HHV-6 infections: The laboratory efficacy and clinical use of ati-HHV-6 agents. In: Elsevier; Amsterdam; 2014:311-331.
43.Singh K, Gangrade A, Jana A, Mandal BB, Das N. Design, Synthesis, Characterization, and Antiproliferative Activity of Organoplatinum Compounds Bearing a 1,2,3-Triazole Ring. ACS Omega. 2019; 4(1):835-841.
44.Shah K, Mujwar S, Gupta JK, Shrivastava SK, Mishra P. Molecular Docking and In Silico Cogitation Validate Mefenamic Acid Prodrugs as Human Cyclooxygenase-2 Inhibitor. Assay Drug Dev Technol. 2019; 17(6):285-291.
45.Rollando R, Warsito W, Masruri M, Widodo N. Potential matrix metalloproteinase-9 inhibitor of aurone compound isolated from Sterculia quadrifida leaves: In-vitro and in-silico studies. Res J Pharm Technol. 2022; 15(11):5250-5254.
46.Al-Salim YM, Al-Asadi RH. Synthesis, Anti-breast Cancer Activity, and Molecular Docking Studies of Thiourea Benzamide Derivatives and Their Complexes with Copper Ion. Trop J Nat Prod Res. 2023; 7(6):3158-3167.
47.Atilgan E, Hu J. Improving Protein Docking Using Sustainable Genetic Algorithms. Int J Comput Inf Syst Ind Manag Appl. 2011; 3:248-255.
48.Wulanawati A, Noviardi H, Ibrohim MSM. Finding a potential Bruceine D inhibitor for apoptotic resistance protein in pancreatic cancer based on molecular docking. Indones J Chem. 2018; 18(3):566-572.
49.Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL. The Structural Basis of Estrogen Receptor/Coactivator Recognition and the Antagonism of This Interaction by Tamoxifen. Cell. 1998;95(7):927-937.