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Tracing the Anti-cancer Mechanism of Pleurotus osteratus by the Integrative Approach of Network Pharmacology and Experimental Studies

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Abstract

The present study identified the probable mechanism behind the anti-cancer activity of the hexane fraction of Pleurotus osteratus (HFPO) using network pharmacology and experimental validation. HFPO myco-metabolites targets and targets related to the cancer were mined from the online web server, and overlapping targets were screened. Out of the 74 overlapping targets, 33 targets were identified in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of cancer. Furthermore, the main active myco-metabolites and hub targets were identified by network analysis of the compound-targets network and protein–protein interaction (PPI), respectively. Molecular docking results showed good binding affinity of the hub targets with their respective myco-metabolites. HFPO induced in-vitro anti-cancer activity by affecting the PI3K-AKT-mTOR pathway, besides time-dependent cell cytotoxicity and apoptotic cell body formation. Additionally, tumor volume reduction was observed in HFPO-treated Ehrlich ascites carcinoma (EAC) bearing Swiss albino mice. Overall, HFPO induces anti-cancer potential by modulating the PI3K-AKT-mTOR signaling pathway.

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Data Availability

Most of the data are available in the main manuscript, and some of the data were supplied in a supplementary file.

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Acknowledgements

Financial assistance provided to SS by the Ministry of Human Resource Development (MHRD), Government of India, as a teaching assistantship is greatly acknowledged.

Funding

This work received financial support as a scholarship to Singh Shreya by the Ministry of Human Resource Development (MHRD), Government of India. Author Alakh N Sahu is thankful to the Department of Biotechnology (DBT), Ministry of Science & Technology, Government of India, New Delhi, India, for providing the funding (Sanction order No. BT/PR25498/NER/95/1223/2017) and for exploring phytochemical and pharmacological evaluations of bioactivity guided fractions of medicinal plants of Tripura.

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Authors and Affiliations

  1. Phytomedicine Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India

    Singh Shreya, Debadatta Mohapatra, Gaurav Gopal Naik & Alakh N. Sahu

  2. Nanomedicine Research Laboratory, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India

    Dulla Naveen Kumar & Ashish Kumar Agarwal

  3. Pharmaceutical Chemistry Research Laboratory II, Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India

    Shivani Jaiswal & Senthil Raja Ayyannan

  4. Department of Biological Sciences, Department of Pharmaceuticals, NIPER-Hyderabad, Telangana, 500037, India

    Santosh Kumar Guru

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  1. Singh Shreya
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Contributions

All authors contributed to the study’s conception and design. Most of the experimental work, material preparation, data collection, data generation through software, analysis, and writing of the original manuscript were performed by Singh Shreya. Dulla Naveen Kumar, Debadatta Mohapatra, Shivani Jaiswal, and Gaurav Gopal Naik contributed to experimentation, data analysis, visualization, validation, formal analysis, editing, and manuscript modifications. Santosh Kumar Guru, Ashish Kumar Agarwal, Senthil Raja Ayyannan, and Alakh N Sahu contributed to conceptualization, investigation, supervision, project administration, reviewing, and editing functions. The first draft of the manuscript was written by Singh Shreya, and all authors commented on previous versions of the manuscript, modified, and approved the final manuscript.

Corresponding author

Correspondence to Alakh N. Sahu.

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Ethics Approval

The study on animals was approved by the Institutional Animal Ethics Committee approval (Protocol no. Dean/2021/IAEC/2553).

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The authors declare no competing interests.

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Shreya, S., Kumar, D.N., Mohapatra, D. et al. Tracing the Anti-cancer Mechanism of Pleurotus osteratus by the Integrative Approach of Network Pharmacology and Experimental Studies. Appl Biochem Biotechnol 195, 152–171 (2023). https://doi.org/10.1007/s12010-022-04111-3

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