ABSTRACT
Cancer as a large group of complex diseases is believed to result from the interactions of numerous genetic and environmental factors but may develop in people without any known genetic or environmental risks, suggesting the existence of other powerful factors to influence the carcinogenesis process. Much attention has been focused recently on particular members of the intestinal microbiota for their potential roles in promoting carcinogenesis. Here we report the identification and characterization of intestinal bacteria that exhibited potent anti-malignancy activities on a broad range of solid cancers and leukemia. We collected fecal specimens from healthy individuals of different age groups (preschool children and university students), inspected their effects on cancer cells, and obtained bacteria with potent anti-malignancy activities. The bacteria mostly belonged to Actinobacteria but also included lineages of other phyla such as Proteobacteria and Firmicutes. In animal cancer models, sterile culture supernatant from the bacteria highly effectively inhibited tumor growth. Remarkably, intra-tumor administration of the bacterial products prevented metastasis and even cleared cancer cells at remote locations from the tumor site. This work demonstrates the prevalent existence of potent malignancy-killers in the human intestinal microbiota, which may routinely clear malignant cells from the body before they form cancers.
Subject(s)
Gastrointestinal Microbiome , Neoplasms/etiology , Adolescent , Adult , Animals , Bacteria/classification , Bacteria/genetics , Bacterial Physiological Phenomena , Cell Survival , Child , Child, Preschool , Disease Models, Animal , Feces/microbiology , Female , Gas Chromatography-Mass Spectrometry , HeLa Cells , Humans , Male , Metagenome , Metagenomics/methods , Mice , Neoplasms/pathology , Phylogeny , RNA, Ribosomal, 16S/genetics , Young AdultABSTRACT
The antibacterial activity and biocompatibility of membranes of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and chitosan (CS) (PHBV)/CS) were evaluated in this study. Maleic anhydride (MA)-grafted polyhydroxyalkanoate (PHBV-g-MA) was evaluated as an alternative to PHBV. Mouse tail skin fibroblasts (FBs) were seeded on two series of these films to assess cytocompatibility. Collagen and cell proliferation analyses indicated that PHBV, PHBV-g-MA and their composite membranes were biocompatible with respect to FB proliferation. However, FB proliferation, collagen production and the percentage of normal cells growing on PHBV/CS membranes were greater than those for PHBV-g-MA/CS membranes. Cell-cycle and apoptosis assays by FBs on the PHBV-series membrane samples were not affected by DNA content related to damage; i.e. rapid apoptosis/necrosis was not observed, demonstrating the potential of PHBV/CS or PHBV-g-MA/CS membranes for biomedical material applications. Moreover, CS-based polysaccharide enhanced the Escherichia coli (BCRC 10239) antibacterial activity of the membranes. Membranes of PHBV-g-MA or PHBV containing CS-based polysaccharide had better antibacterial activity.
