Unveiling the anticancer potential and toxicity of Ganoderma applanatum wild mushroom derived bioactive compounds: An in vitro, in vivo and in silico evaluation

This study explores the anticancer potential of methanolic extract from Ganoderma applanatum, focusing on its cytotoxicity across various cancer cell lines and its safety and efficacy in an in vivo hepatocellular carcinoma (HCC) model, along with molecular docking analysis of its bioactive compounds targeting B-cell lymphoma 2 (Bcl-2) protein. The MTT assay revealed significant cytotoxicity of the extract against epidermoid carcinoma (A431), human alveolar carcinoma (A549), and hepatocellular carcinoma (HepG2) cell lines, with the extract exhibiting the highest potency (IC50 of 95.65 µg/ml) against HepG2 cells. Apoptosis induction and DNA degradation in HepG2 cells were confirmed through mitochondrial membrane potential analysis, ethidium bromide/acridine orange staining, and DNA fragmentation assays. In vivo studies on Wistar albino rats showed that administration of the extract up to 1000 mg/ml did not significantly affect body weight or hematological parameters, suggesting a favorable safety profile. Histopathological examination revealed normal liver architecture at most doses, with mild inflammation observed at the highest dose (1000 mg/ml). The G. applanatum extract were showed reducing liver weight and improving body weight in a Diethylnitrosamine (DEN)-induced HCC model was comparable to cyclophosphamide, indicating its potential as a less toxic alternative or adjunct to conventional chemotherapy. Additionally, the extract reduced elevated serum liver enzymes, demonstrating hepatoprotective effects. Molecular docking of nine bioactive compounds from G. applanatum identified 2h-3,11c-(epoxymethano)phenanthro[10,1-bc]pyran as a promising candidate for further investigation. These findings suggest G. applanatum as a novel anticancer agent with the potential for natural, effective cancer therapy.