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<p><i>Cordyceps militaris</i>, a medicinal mushroom in traditional Chinese medicine, emerged as a promising source of bioactive compounds, exhibiting potent antioxidant, anti-inflammatory, anticancer, antiviral and immunomodulatory properties. Despite documenting in vitro cytotoxicity against various cancer cell lines, in vivo efficacy against Dalton’s Lymphoma (DL) remains underexplored. This study investigates the anticancer efficacy of methanolic <i>Cordyceps militaris</i> extract (CME) against DL-bearing mice, and validate its molecular mechanism <i>via </i>in-silico approaches. DL-bearing Swiss albino mice treated with varying doses of CME showed significant tumor volume reduction and improved survival rates and cytotoxicity. Apoptosis induction, cell cycle progression, mitochondrial membrane potential and DNA fragmentation were analyzed using AO/EB dual staining, flow cytometry, Rhodamine-123 and comet assay, respectively. Molecular docking and dynamics simulations were performed to validate the interactions of CME’s potent bioactive compound, cordycepin with anti-apoptotic target proteins, BCL-2, BCL-xL and BFL-1. CME treatment (24–96&#xa0;h) led to dose- and time-dependent apoptosis supported by scanning electron microscopy, G2/M phase arrest, mitochondrial membrane depolarization and substantial DNA damage characterized by increased tail length, % tail DNA and olive tail moment in comet assay. Docking and MD simulations established strong and stable binding affinity of cordycepin to BFL-1 throughout 100ns simulation time, corroborating in vivo apoptotic outcomes. CME induces mitochondria-mediated apoptosis, DNA damage and cell cycle arrest in DL cells. This highlights the potential of <i>C. militaris</i> as a natural anticancer drug against lymphoma, thereby warranting further clinical validation for phytotherapeutic applications.</p>

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Deciphering the anticancer potential of an entomopathogenic fungus, Cordyceps militaris in Dalton’s Lymphoma transplanted murine model: a multidimensional approach involving computational methods and in vivo validation

  • 期刊论文

  • 发表日期：

    2026年5月25日

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  • Diksha Dutta,
  • Akalesh Kumar Verma,
  • Namram Sushindrajit Singh,
  • Dhrubajyoti Gogoi,
  • Partha Pratim Dutta

摘要

Cordyceps militaris, a medicinal mushroom in traditional Chinese medicine, emerged as a promising source of bioactive compounds, exhibiting potent antioxidant, anti-inflammatory, anticancer, antiviral and immunomodulatory properties. Despite documenting in vitro cytotoxicity against various cancer cell lines, in vivo efficacy against Dalton’s Lymphoma (DL) remains underexplored. This study investigates the anticancer efficacy of methanolic Cordyceps militaris extract (CME) against DL-bearing mice, and validate its molecular mechanism via in-silico approaches. DL-bearing Swiss albino mice treated with varying doses of CME showed significant tumor volume reduction and improved survival rates and cytotoxicity. Apoptosis induction, cell cycle progression, mitochondrial membrane potential and DNA fragmentation were analyzed using AO/EB dual staining, flow cytometry, Rhodamine-123 and comet assay, respectively. Molecular docking and dynamics simulations were performed to validate the interactions of CME’s potent bioactive compound, cordycepin with anti-apoptotic target proteins, BCL-2, BCL-xL and BFL-1. CME treatment (24–96 h) led to dose- and time-dependent apoptosis supported by scanning electron microscopy, G2/M phase arrest, mitochondrial membrane depolarization and substantial DNA damage characterized by increased tail length, % tail DNA and olive tail moment in comet assay. Docking and MD simulations established strong and stable binding affinity of cordycepin to BFL-1 throughout 100ns simulation time, corroborating in vivo apoptotic outcomes. CME induces mitochondria-mediated apoptosis, DNA damage and cell cycle arrest in DL cells. This highlights the potential of C. militaris as a natural anticancer drug against lymphoma, thereby warranting further clinical validation for phytotherapeutic applications.