Microbial and Natural Metabolites That Inhibit Splicing: A Powerful Alternative for Cancer Treatment.
In eukaryotes, genes are frequently interrupted with noncoding sequences named introns. Alternative splicing is a nuclear mechanism by which these introns are removed and flanking coding regions named exons are joined together to generate a message that will be translated in the cytoplasm. This mechanism is catalyzed by a complex machinery known as the spliceosome, which is conformed by more than 300 proteins and ribonucleoproteins that activate and regulate the precision of gene expression when assembled. It has been proposed that several genetic diseases are related to defects in the splicing process, including cancer. For this reason, natural products that show the ability to regulate splicing have attracted enormous attention due to its potential use for cancer treatment. Some microbial metabolites have shown the ability to inhibit gene splicing and the molecular mechanism responsible for this inhibition is being studied for future applications. Here, we summarize the main types of natural products that have been characterized as splicing inhibitors, the recent advances regarding molecular and cellular effects related to these molecules, and the applications reported so far in cancer therapeutics.
Laboratorio de Ecología Molecular Microbiana, Centro de Investigaciones en Ciencias Microbiológicas, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Edificio IC11, Ciudad Universitaria, 72570 Colonia San Manuel, PUE, Mexico.
Nancy
0000-0003-4645-2371
N
Martínez-Montiel
Laboratorio de Bioquímica y Biología Molecular, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Edificio 103H, Ciudad Universitaria, 72550 Colonia San Manuel, PUE, Mexico; Posgrado en Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Edificio 105 I, Ciudad Universitaria, 72570 Colonia San Manuel, PUE, Mexico.
Nora Hilda
NH
Rosas-Murrieta
Laboratorio de Ecología Molecular Microbiana, Centro de Investigaciones en Ciencias Microbiológicas, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Edificio IC11, Ciudad Universitaria, 72570 Colonia San Manuel, PUE, Mexico.
Mónica
M
Martínez-Montiel
Laboratorio de Ecología Molecular Microbiana, Centro de Investigaciones en Ciencias Microbiológicas, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Edificio IC11, Ciudad Universitaria, 72570 Colonia San Manuel, PUE, Mexico.
Mayra Patricia
MP
Gaspariano-Cholula
Laboratorio de Ecología Molecular Microbiana, Centro de Investigaciones en Ciencias Microbiológicas, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Edificio IC11, Ciudad Universitaria, 72570 Colonia San Manuel, PUE, Mexico.
Rebeca D
0000-0002-2085-085X
RD
Martínez-Contreras
D017398:Alternative Splicing / Q000187:drug effects*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D011714:Pyrans / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D005233:Fatty Alcohols; D011714:Pyrans; C076087:herboxidiene