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Anti-proliferative effect of leaf phytochemicals of soursop (Annona muricata L.) against human osteosarcoma in vitro

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Abstract

Leaves of soursop (Annona muricata) is a potential anti-cancer agent. However, there is no report on the effect of soursop leaf phytochemicals against osteosarcoma, a musculoskeletal cancer commonly affecting children and adults. The current study identified 28 metabolites from ethyl acetate leaf (EAL) extract through GC–MS chemoprofiling and subjected to in silico analysis against the potential protein target, platelet-derived growth factor receptor α (PDGFRA) of osteosarcoma, including absorption, distribution, metabolism, and excretion and toxicity (ADMET) analysis to identify the possible hit compounds. This resulted in three hit leaf bioactives, namely 2’-hydroxy-5’-methyl chalcone, linoleic acid and annonacin showing good binding affinity with a docking score of − 7.4, − 7.0 and − 6.9 kcal/mol, respectively. With ADMET analysis, 2’-hydroxy-5’-methyl chalcone and linoleic acid obeyed Lipinski’s rule of five, whereas annonacin showed a slight violation. Among the three docked complexes, annonacin shows good stability during molecular dynamic simulation performed with PDGFRA. The concentration of the key marker compound, annonacin in EAL concentrate is found to be 5.032 ± 0.13 mg/g of leaf sample and is used for cytotoxicity assessment. Further, EAL concentrate exhibits cytotoxicity (IC50 value) on MG-63 osteosarcoma cells in vitro for concentrations ranging from 10 to 25 µg/mL. Nuclear imaging of osteoblast cells treated with EAL concentrate at 25 µg/mL concentration shows typical symptoms of apoptosis. In vitro cytotoxicity along with nuclear imaging confirmed EAL concentrate from soursop to be a potential drug candidate in developing new anti-cancer agent against osteosarcoma.

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Data availability

The authors declare that data supporting the findings of this study are available within the article inclusive of supplementary information.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Centre for Agricultural Nanotechnology, Tamil Nadu Agricultural University, Coimbatore, 641 003, India

    Haripriya Shanmugam

  2. Tissue Engineering Laboratory, PSG Institute of Advanced Studies, Coimbatore, 641 004, India

    R. Narmadha & R. Selvakumar

  3. Centre for Plant Molecular Biology and Biotechnology, Tamil Nadu Agricultural University, Coimbatore, 641 003, India

    Caroline Ravikumar, Kiruthika Ariyaperumal & Jayakanthan Mannu

Authors
  1. Haripriya Shanmugam
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  2. R. Narmadha
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  3. Caroline Ravikumar
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  4. Kiruthika Ariyaperumal
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  5. R. Selvakumar
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  6. Jayakanthan Mannu
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Contributions

HS conceptualized and planed the study. HS sourced, extracted and characterized leaf extract of soursop used in this study at CANT, TNAU. CR, KA and JM carried out molecular interaction studies at CPMBB, TNAU. RN and RS carried out in vitro anti-proliferative activity in MG-63 cancer cells at PSG IAS, Coimbatore. HS drafted the final version of the manuscript and all authors approved the same.

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Correspondence to Haripriya Shanmugam.

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Shanmugam, H., Narmadha, R., Ravikumar, C. et al. Anti-proliferative effect of leaf phytochemicals of soursop (Annona muricata L.) against human osteosarcoma in vitro. Chem. Pap. 78, 3787–3797 (2024). https://doi.org/10.1007/s11696-024-03349-x

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