Anti-cancer effect of Loranthus micranthus via downregulation of inflammation, tryptophan catabolism and kynurenine synthesis

Abstract

New therapeutic approaches are essential in the fight against breast cancer, which remains one of the top causes of mortality globally. Innovative and efficient methods of treating and preventing cancer has become expedient since its incidence rates are rising globally. Combining herbal extracts and chemotherapy have drawn a lot of attention in recent times as a cutting-edge cancer prevention approach. The wild parasitic plant Loranthus micranthus is extensively distributed throughout the world and is well-known for its therapeutic uses. Previous preclinical investigations indicated that the leaves and stem extracts of L. micranthus had the potential to suppress breast cancer. Investigating the anticancer effects of L. micranthus extracts through network pharmacology analysis, in vitro and in vivo experiments is the goal of the current study. Network pharmacology analysis revealed 207 targets and 30 bioactive phytoconstituents of L. micranthus associated with the metabolism of breast cancer. L. micranthus controlled the metabolism of tryptophan and nitrogen in breast cancer, according to KEGG analysis and in silico models. The results of the experiment showed that L. micranthus significantly reduced the synthesis of kynurenine in interferon-γ (IFN-γ)-stimulated breast cancer cells, downregulated important proteins involved in tryptophan catabolism, and produced no cytotoxic effects in human breast cancer cells (MCF 7 and MDA-MB 231) at the administered doses. The viability of T cells co-cultured with IFN-γ-treated breast cancer cells was also markedly enhanced by L. micranthus pre-treatment. The in vivo investigation showed a similar outcome, with L. micranthus treatment suppressing the inflammatory response, IDO activity/expression, lowering kynurenine levels, blocking CTLA-4 immune checkpoint and finally increasing the CD4⁺ T cell population in rats with DMBA-induced breast cancer.

Keywords: Breast cancer; Immunotherapy; Inflammation; Kynurenine; Loranthus micranthus; Tryptophan catabolism.