Chrysomycin A Inhibits the Proliferation, Migration and Invasion of U251 and U87-MG Glioblastoma Cells to Exert Its Anti-Cancer Effects

Abstract

Chrysomycin A (Chr-A), an antibiotic from Streptomyces, is reported to have anti-tumor and anti-tuberculous activities, but its anti-glioblastoma activity and possible mechanism are not clear. Therefore, the current study was to investigate the mechanism of Chr-A against glioblastoma using U251 and U87-MG human cells. CCK8 assays, EdU-DNA synthesis assays and LDH assays were carried out to detect cell viability, proliferation and cytotoxicity of U251 and U87-MG cells, respectively. Transwell assays were performed to detect the invasion and migration abilities of glioblastoma cells. Western blot was used to validate the potential proteins. Chr-A treatment significantly inhibited the growth of glioblastoma cells and weakened the ability of cell migration and invasion by down regulating the expression of slug, MMP2 and MMP9. Furthermore, Chr-A also down regulated Akt, p-Akt, GSK-3β, p-GSK-3β and their downstream proteins, such as β-catenin and c-Myc in human glioblastoma cells. In conclusion, Chr-A may inhibit the proliferation, migration and invasion of glioblastoma cells through the Akt/GSK-3β/β-catenin signaling pathway.

Chrysomycin a Regulates Proliferation and Apoptosis of Neuroglioma Cells via Akt/GSK-3β Signaling Pathway In Vivo and In Vitro

“…In our study, remarkable downregulation of p-Akt and p-GSK-3β in Chr-A group was observed with Chr-A treatment, and their downstream, slug and MMP2, were also showed a significant decrease. Taken our previous work in vitro [14] together, Chr-A may function against glioblastoma via apoptosis regulation by Akt/GSK -3β signaling pathway confirming the KEGG enrichment analysis above.…”

“…Chr-A has a group of benzonaphthopyranone glycosides, suggested to possess antitumor activity [8]. And it did show inhibitory effect to human U251 and U87-MG glioblastoma cells in vitro [14]. In the current study, we verified the antitumor activity of Chr-A in vivo using human U87-MG cells xenograft glioblastoma model, from which we found that intraperitoneal administration of both 3 and 10 mg/kg Chr-A suppressed the tumorigenicity.…”

“…neuroinflammation properties [11][12][13]. Previously, the inhibitory effect and possible mechanisms of Chr-A on proliferation, migration and invasion towards U251 and U87 glioblastoma cells has been investigated [14]. However, there is few reports on the mechanism of Chr-A exerting antiglioblastoma effect in vivo.…”

Redefining bioactive small molecules from microbial metabolites as revolutionary anticancer agents

“…IRD-009 HCT-116 cells (colorectal cancer) Cell cycle modulator (G 0 /G 1 phase arrest), induction of apoptosis via DNA double strand interaction and damage [ 92 ] Prodigiosin Tripyrrole Pigment Serratia marcescens MDA-MB-231 cells and xenograft (breast cancer), MDA-MB-468 cells (breast cancer) Induction of apoptosis and downregulation of HSP90α. Suppression of migration and invasion and induction of apoptosis and via inhibition of Wnt/ β-catenin signaling [ 93 , 94 ] Pyocin S2 Bacteriocin Pseudomonas aeruginosa HepG2 cells (hepatocellular carcinoma), IM-9 cells (B-lymphoblastoid cell line) Induction of cell death [ 95 ] Pyocyanin Phenazine Pigment Pseudomonas aeruginosa MCF7 cells (breast cancer) Induction of apoptosis and necrosis [ 96 ] Rebeccamycin/NSC 655649 Indocarbozole Lechevalieria aerocoloigenes, Saccharothrix aerocolonigenes P388 cells (leukemia), L1210 cells (leukemia), B16 tumor model (melanoma), A549 xenograft (lung adenocarcinoma), Intercalates with DNA, promotes double strand breakage, inhibits topoisomerase I [ 97 , 98 ] Resistomycin Pentacyclic Polyketide Antibiotic Streptomyces aurantiacus AAA5 HepG2 cells (hepatocellular carcinoma), HeLa cells (cervical cancer), MDA-MB-231 xenograft (breast cancer), patient derived xenograft (breast cancer) Induction of cell death. Suppression of tumor progression, metastasis, and invasion by Pellino-1 inhibition and SNAIL/SLUG degradation [ 99 , 100 ] Salinomycin Carboxylic Polyether Ionophore Streptomyces albus OVCAR-8 (ovarian cancer), mammary cancer stem cells, patient -derived CLL cells Induction of apoptosis and G1 cell cycle arrest via Skp2 destabilization and Stat...…”

Killing of Staphylococcus aureus persisters by a multitarget natural product chrysomycin A

“…1A) (19). ChryA belongs to the gilvocarcin family of C-aryl glycoside natural products (20) and shows various biological activities, including antibacteriophage (19), antibacterial (21)(22)(23)(24), antitumor (25,26), and antineuroinflammatory activities (27), implying its considerable potential as a multiple-target agent. Analogous compounds of ChryA, such as gilvocarcins, ravidomycins, and polycarcins, are also known as antibacterial and antitumor chemicals (21,28).…”