The disulphide cleavage derivative (C42-4) of 11′-deoxyverticillin A (C42) fails to induce apoptosis and genomic instability in HeLa cells

Our previous study revealed 11'-deoxyverticillin A (C42), a natural product isolated from the Ophiocordyceps-associated fungus Clonostachys rogersoniana and a member of the epipolythiodioxopiperazines (ETPs), induced both apoptosis and autophagy in HCT116 cells; however, the role of disulphide/...

Full description

Saved in:
Bibliographic Details
Published in:Mycology 2023-10, Vol.14 (4), p.358-370
Main Authors: Hou, Bolin, Yang, Huaiyi, Li, Erwei, Jiang, Xuejun
Format: Article
Language:English
Subjects:
Actin
Apoptosis
Autophagy
Bridge failure
C42
C42-4
Caspase-3
Cleavage
Deoxyribonucleic acid
Disulfides
DNA
DNA damage
DNA repair
Gene expression
Genomic instability
Histone H2A
Micronuclei
Natural products
nuclear stability
Phagosomes
Poly(ADP-ribose) polymerase
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Our previous study revealed 11'-deoxyverticillin A (C42), a natural product isolated from the Ophiocordyceps-associated fungus Clonostachys rogersoniana and a member of the epipolythiodioxopiperazines (ETPs), induced both apoptosis and autophagy in HCT116 cells; however, the role of disulphide/polysulphide bridges of C42 in the regulation of autophagy remains unexplored. Here, we revealed that C42 activated both caspase-dependent apoptosis and autophagy in HeLa cells, whereas its disulphide cleavage derivative C42-4 failed to induce the cleavage of both caspase-3 and PARP-1. In contrast, both C42 and C42-4 increased the formation of autophagosomes, punctate staining of LC3, and the ratio of LC3-II to actin, suggesting that disulphide/polysulphide bridges are dispensable for the induction of the autophagic process. Moreover, we found that C42 but not C42-4 led to nuclear instability by increasing the formation of micronuclei and expression of phosphorylated histone H2AX (γ-H2AX), a widely used marker for DNA double strand breaks (DSBs), while Rad51, a protein pivotal for DNA repair, was decreased upon challenge with C42. These results demonstrate that the disulphide bonds in ETPs play an essential role in the induction of caspase-dependent apoptosis and nuclear stability.
ISSN:2150-1203
2150-1211
DOI:10.1080/21501203.2023.2248168