ABSTRACT
The roles of gut microorganisms in cancer are diverse. Studies on metagenomics and bioinformatics have documented diverse microbial etiology in different tumors. Evidence supports that a commensal microbiome could provide a promising strategy to treat and prevent cancer through interference in several biologic processes, such as host cell survival and death, host immune function, inflammation, oncogenic signaling, and several hormone receptor signaling and detoxification pathways. The cumulative evidence recommends that metabolites of commensal gut microorganisms (e.g., short-chain fatty acids, omega-3 and -6 fatty acids) play an important role in cancer prevention, with a robust antiproliferative effect of omega-3 fatty acids. Intriguingly, the endocannabinoid system (omega-3 and -6 fatty acid-derived neurotransmitter of the body) shows diverse effects on cancer prevention and oncogenesis depending on the context of the tumor microenvironment. Thus, an interplay of gut microorganisms with their fatty acid metabolites and the endocannabinoid system play an important role in the development, progression, immunomodulation, and chemoresistance of cancer. In this review, we highlight aspects of the current knowledge of and interactions between the microbiome with fatty acids and the host endocannabinoid system. We also document their effect on host immunomodulation and chemoresistance, and discuss how these insights might translate into future development of microbiome-targeted therapeutic interventions.
Subject(s)
Fatty Acids, Omega-3 , Gastrointestinal Microbiome , Neoplasms , Humans , Endocannabinoids/pharmacology , Fatty Acids/pharmacology , Drug Resistance, Neoplasm , Fatty Acids, Volatile/metabolism , Immunomodulation , Immunity , Fatty Acids, Omega-3/pharmacology , Neoplasms/drug therapy , Tumor MicroenvironmentABSTRACT
Well-established, traditional Kumada cross-couplings involve preformed Grignard reagents in dry ethereal solvent that typically react, e.g., with aryl halides via Pd catalysis to afford products of net substitution. Therefore, in the work described, which appears to be counterintuitive, exposure of these same aromatic halides to catalytic amounts of Pd(II) and excess magnesium metal in pure water leads to symmetrical/unsymmetrical biaryls, indicative of a net Kumada-like biaryl coupling. Evidence is presented suggesting that Grignard reagents, formed in situ in water, may be involved.
Subject(s)
Hydrocarbons, Brominated/chemistry , Hydrocarbons, Cyclic/chemistry , Hydrocarbons, Iodinated/chemistry , Magnesium/chemistry , Palladium/chemistry , Catalysis , Water/chemistryABSTRACT
A mild and environmentally attractive dehalogenation of functionalized aryl halides has been developed using nanoparticles formed from PdCl2 in the presence of tetramethyldisiloxane (TMDS) on water. The active catalyst and reaction medium can be recycled. This method can also be applied to cascade reactions in a one-pot sequence.
Subject(s)
Hydrocarbons, Brominated/chemistry , Hydrocarbons, Chlorinated/chemistry , Palladium/chemistry , Catalysis , Combinatorial Chemistry Techniques , Molecular Structure , Siloxanes/chemistry , Water/chemistryABSTRACT
Organic-solvent-free cross-couplings between benzylic and alkenyl halides have been developed. Various alkenyl halides can be efficiently benzylated by combining the precursor halides in the presence of Zn dust and a Pd catalyst at room temperature, in water as the only medium.