Biogenic synthesis of gold nanoparticles using Coleus forskohlii leaf extract enhances anticancer activity against HT-29 cells and modulates the p53 regulated immune microenvironment in colon adenocarcinoma

Colorectal cancer remains a leading cause of cancer-related mortality worldwide, underscoring the urgent need for novel therapeutic strategies. In this study, we hypothesized that the synergistic combination of Coleus forskohlii leaf extract (CFLE) and its biogenically synthesized nanogold would enhance anticancer efficacy against HT-29 human colon adenocarcinoma cells by modulating reactive oxygen species (ROS) production and activating the tumor suppressor protein p53. Aqueous CFLE was prepared from dried leaves and used to synthesize gold nanoparticles, which were characterized by UV-Vis spectrophotometry, X-ray diffraction (XRD), and Fourier-transform infrared (FT-IR) spectroscopy. FT-IR analysis confirmed the presence of bioactive phytochemicals in CFLE capable of reducing and stabilizing the nanogold. Both CFLE and CFLE + nanogold demonstrated dose-dependent inhibition of HT-29 cell viability, accompanied by elevated ROS levels and significant upregulation of p53 expression. Combining of CFLE with the nanogold (extract + nanogold) could cancel the toxic effects of gold nanoparticles. Complementary bioinformatic analyses of colon adenocarcinoma datasets revealed that high TP53 expression correlates with improved patient survival and enhanced immune infiltration, particularly of B plasma cells, neutrophils, and M2 macrophages, mediated through chemokine signaling pathways. Our findings highlight the dual anticancer and antimicrobial potential of CFLE and CFLE + nanogold, with the nanocomposite formulation offering a novel, plant-based approach to colon cancer therapy through ROS-mediated p53 activation. In addition, CFLE could pause the toxic effects of the gold nanoparticles. This work positions TP53 not only as a central mechanistic node in CFLE + nanogold-induced cytotoxicity but also as a robust prognostic biomarker in colorectal cancer.