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Beneficial Proapoptotic Effect of Heterobasidion Annosum Extract in Colorectal Cancer Xenograft Mouse Model
Anna Sadowska1, Diana Sawicka1, Katarzyna Godlewska1,2
1Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna 37, 15-295 Bialystok, Poland.
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.
Insights
The fungal extract Heterobasidion annosum (HA) demonstrated anticancer effects against colorectal cancer in mice, reducing tumor volume and inducing apoptosis. Combined with 5-fluorouracil (5FU), HA extract shows promise for further antitumor research.
Area of Science:
- Mycology
- Oncology
- Pharmacology
Background:
- Fungal extracts show promise for anticancer therapies.
- Colorectal cancer remains a significant global health challenge.
- Investigating novel natural compounds for cancer treatment is crucial.
Purpose of the Study:
- To evaluate the antitumor activity of Heterobasidion annosum (HA) extract in a colorectal cancer mouse model.
- To assess the effects of HA extract, alone and in combination with 5-fluorouracil (5FU), on tumor growth and apoptosis.
- To analyze key apoptotic markers and proliferation indicators.
Main Methods:
- An in vivo colorectal cancer model using DLD-1 human cancer cells implanted in mice.
- Administration of HA extract, 5FU, or a combination therapy.
- Measurement of tumor volume, serum analysis of apoptotic proteins (caspase-8, caspase-3, p53, Bcl-2, survivin) via ELISA, and immunohistochemical assessment of Ki-67.
Main Results:
- Tumor volumes were significantly reduced in groups treated with 5FU and/or HA extract compared to the control group.
- Combined 5FU and HA extract administration increased concentrations of caspase-8 and p53.
- Survivin and Bcl-2 levels decreased in all treatment groups; Ki-67 was positive in all groups.
Conclusions:
- Heterobasidion annosum extract exhibits significant antitumor effects against colorectal cancer in vivo.
- The HA extract, particularly in combination with 5FU, induces apoptosis and reduces tumor growth.
- These findings support further investigation into HA extract as a potential adjuvant therapy for colorectal cancer.
