Enhanced anticancer effect of cetuximab combined with ethanol extract of Volvariella volvacea in colorectal cancer targeted TOP2A and PPARγ

Context: Colorectal cancer (CRC) is a major global health concern as innovative therapeutic strategies to enhance treatment outcomes. This study investigates the therapeutic potential of the ethanol extract derived from Volvariella volvacea in combination with cetuximab for CRC. Aims: To evaluate the inhibition of topoisomerase II alpha (TOP2A) and include the peroxisome proliferator-activated receptor gamma (PPARγ), a key regulator of cell growth and differentiation. Methods: The method used computational modeling and molecular docking to assess the binding affinities and interactions between the bioactive components, cetuximab, TOP2A, and PPARγ. In vitro experiments were conducted using CRC cell lines. Cells were treated with cetuximab alone or in combination with V. volvacea extract. Cell viability and immunofluorescence were conducted to evaluate the effect of combination therapy on TOP2A and PPARγ. Results: The results unveiled compelling binding interactions, suggesting the potential for dual targeting of TOP2A and PPARγ. The results demonstrated a reduction in cell viability, downregulation of TOP2A, and modulation of PPARγ. These findings indicate the potential of V. volvacea extract as an adjuvant therapy to cetuximab in CRC. Targeting both TOP2A and PPARγ enhances the efficacy of CRC treatment. Conclusions: Moreover, it highlights the importance of harnessing natural compounds and molecular insights to develop innovative combinatorial therapies for complex diseases like CRC.