Beneficial Proapoptotic Effect of Heterobasidion Annosum Extract in Colorectal Cancer Xenograft Mouse Model

Molecules. 2023 Jan 31;28(3):1352. doi: 10.3390/molecules28031352.

Abstract

Fungal extracts possess potential anticancer activity against many malignant neoplastic diseases. In this research, we focused on the evaluation of Heterobasidion annosum (HA) extract in colorectal cancer in an in vivo model. The mice with implanted DLD-1 human cancer cells were given HA extract, the referential drug-5-fluorouracil (5FU), or were treated with its combination. Thereafter, tumor volume was measured and apoptotic proteins such as caspase-8, caspase-3, p53, Bcl-2, and survivin were analyzed in mice serum with an ELISA assay. The Ki-67 protein was assessed in tumor cells by immunohistochemical examination. The biggest volumes of tumors were confirmed in the DLD-1 group, while the lowest were observed in the population treated with 5FU and/or HA extract. The assessment of apoptosis showed increased concentrations of caspase 8 and p53 protein after the combined administration of 5FU and HA extract. The levels of survivin and Bcl-2 were decreased in all tested groups compared to the DLD-1 group. Moreover, we observed a positive reaction for Ki-67 protein in all tested groups. Our findings confirm the apoptotic effect of extract given alone or with 5FU. The obtained results are innovative and provide a basis for further research concerning the antitumor activity of the HA extract, especially in the range of its interaction with an anticancer chemotherapeutic agent.

Keywords: Heterobasidion annosum; apoptosis; colon cancer.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Humans
  • Ki-67 Antigen
  • Mice
  • Proto-Oncogene Proteins c-bcl-2
  • Survivin
  • Tumor Suppressor Protein p53*
  • Xenograft Model Antitumor Assays

Substances

  • Fluorouracil
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Survivin
  • Tumor Suppressor Protein p53

Supplementary concepts

  • Heterobasidion annosum