2. Academic Validation
  3. Biotransformation of steroid hormones by intestinal fungi and their special cytotoxicity on HeLa cancer cells

Biotransformation of steroid hormones by intestinal fungi and their special cytotoxicity on HeLa cancer cells

  • Bioorg Chem. 2025 Nov:166:109102. doi: 10.1016/j.bioorg.2025.109102.
Manman Tian 1,  Chaoyan Han 2,  Yajie Hu 3,  Shengqiao Luan 2,  Xiangge Tian 4,  Ping Guo 5,  Xiangwan Li 3,  Linlin Sui 2,  Chao Wang 6,  Xiaochi Ma 7,  Dawei Li 8
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China; Second Affiliated Hospital, Dalian Medical University, Dalian 116023, PR China.
  • 2 College of Pharmacy, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, PR China.
  • 3 The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China.
  • 4 Second Affiliated Hospital, Dalian Medical University, Dalian 116023, PR China.
  • 5 College of Pharmacy, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, PR China. Electronic address: [email protected].
  • 6 The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China; College of Pharmacy, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, PR China.
  • 7 Second Affiliated Hospital, Dalian Medical University, Dalian 116023, PR China. Electronic address: [email protected].
  • 8 The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China. Electronic address: [email protected].
PMID: 41106073 DOI: 10.1016/j.bioorg.2025.109102
Abstract

Steroid Hormones play an important role in the maintenance and progression of Cancer. This study explored the biotransformation of nandrolone and testosterone by human intestinal Fungal strains (Syncephalastrum monosporum PYS2703, Aspergillus japonicus Y4009A, Rhizopus microsporus PT2906, Aspergillus niger RG13B1) in vitro. A total of twenty-two metabolites were identified, including eight novel compounds (1-7, 13) and fourteen known analogs (8-12, 14-22). The structures of all metabolites were determined via NMR and HRESIMS spectroscopic techniques. The structural analysis revealed that hydroxylation and oxidation were the primary biotransformation reactions. In addition, metabolites (1-29), including those derived from norethisterone biotransformation by Rhizopus microsporus PT2906 in a previous study (metabolites 23-29), displayed special cytotoxicity on cervical Cancer HeLa cells. Among these, 6,7-didehydronorethisterone (26), exhibited the most remarkable anti-tumor activity, which was achieved by inducing Apoptosis through modulating the p53 signaling pathway. Additionally, the study results suggested that compound 26 may interact with the THR-256 and GLU-258 residues of p53 via hydrogen bonds. In conclusion, intestinal fungi play an important role in the metabolism of steroid hormones: they can biotransform nandrolone and testosterone into various derivatives, which can serve as crucial resources for Cancer treatment.

Keywords

Biotransformation; Hela cancer cell; Intestinal fungi; Steroid hormones; p53 signaling pathway.

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