title: Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases.
abstract: Autophagy has been referred to as a double-edged sword in tumorigenesis and tumor progression. Emerging evidence suggests that pharmacological modulation of autophagy is a promising therapeutic strategy for cancer. However, few autophagy-modulating compounds are currently approved for clinical use in humans. Matrine is a natural compound extracted from traditional Chinese medicine that is widely used for treatment of a variety of diseases without any obvious side effects. Recently, matrine has been reported to induce autophagy and autophagic cell death in cancer cells, although the underlying mechanisms have yet to be elucidated. Here, we systematically examined the autophagic events induced by matrine in SGC7901 cells. The accumulation of autophagic vacuoles in matrine-treated cells was verified by the conversion of microtubule-associated protein light chain 3 as well as confocal and transmission electron microscopy. Furthermore, we demonstrated that matrine blocked autophagic degradation by impairing the activities of lysosomal proteases. Moreover, confocal microscopy and gradient ultracentrifugation revealed that the trafficking processes and proteolytic activation of cathepsins were inhibited by matrine. Using a pH sensor probe, we found elevated pH values in endosomes/lysosomes in response to matrine treatment. Therefore, matrine seems to be a novel autophagy inhibitor that can modulate the maturation process of lysosomal proteases.
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences,  Beijing 101318, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Xing
authors.forename: Chongqin
authors.initials: C
authors.lastname: Yi
authors.forename: Huishan
authors.initials: H
authors.lastname: Zhu
authors.forename: Xianwei
authors.initials: X
authors.lastname: Chen
authors.forename: Jiao
authors.initials: J
authors.lastname: Guo
authors.forename: Weixin
authors.initials: W
authors.lastname: Guo
authors.forename: Wenmei
authors.initials: W
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.forename: Youyong
authors.initials: Y
authors.lastname: Lu
authors.forename: Siqi
authors.initials: S
authors.lastname: Liu
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004789:Enzyme Activation; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D059748:Proteolysis; D011807:Quinolizines / Q000494:pharmacology*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D017931:DNA Primers; D011807:Quinolizines; D010447:Peptide Hydrolases; D000093842:Matrines