EMAIL THIS PAGE TO A FRIEND

PloS one

Cucurbitacin B induced ATM-mediated DNA damage causes G2/M cell cycle arrest in a ROS-dependent manner.


PMID 24505404

Abstract

Cucurbitacins are a class of triterpenoids widely distributed in plant kingdom with potent anti-cancer activities both in vitro and in vivo by inducing cycle arrest, autophagy, and apoptosis. Cucurbitacin B (Cuc B), could induce S or G2/M cell cycle arrest in cancer cells while the detailed mechanisms remain to be clear. This study was designed to precisely dissect the signaling pathway(s) responsible for Cuc B induced cell cycle arrest in human lung adenocarcinoma epithelial A549 cells. We demonstrated that low concentrations of Cuc B dramatically induced G2/M phase arrest in A549 cells. Cuc B treatment caused DNA double-strand breaks (DSBs) without affecting the signal transducer and activator of transcription 3 (STAT3), the potential molecular target for Cuc B. Cuc B triggers ATM-activated Chk1-Cdc25C-Cdk1, which could be reversed by both ATM siRNA and Chk1 siRNA. Cuc B also triggers ATM-activated p53-14-3-3-σ pathways, which could be reversed by ATM siRNA. Cuc B treatment also led to increased intracellular reactive oxygen species (ROS) formation, which was inhibited by N-acetyl-l-cysteine (NAC) pretreatment. Furthermore, NAC pretreatment inhibited Cuc B induced DNA damage and G2/M phase arrest. Taken together, these results suggested that Cuc B induces DNA damage in A549 cells mediated by increasing intracellular ROS formation, which lead to G2/M cell phase arrest through ATM-activated Chk1-Cdc25C-Cdk1 and p53-14-3-3-σ parallel branches. These observations provide novel mechanisms and potential targets for better understanding of the anti-cancer mechanisms of cucurbitacins.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

1009005
Acetylcysteine, United States Pharmacopeia (USP) Reference Standard
C5H9NO3S
A0150000
Acetylcysteine, European Pharmacopoeia (EP) Reference Standard
C5H9NO3S
GW21178 Anti-ATM antibody produced in chicken, affinity isolated antibody, buffered aqueous solution
SAB3500147
Anti-ATM antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB4501968
Anti-ATM antibody produced in rabbit, affinity isolated antibody
A6218 Anti-ATM antibody, Mouse monoclonal, clone SYML6A10, purified from hybridoma cell culture
A6093 Anti-ATM antibody, Mouse monoclonal, clone SYR6D4, purified from hybridoma cell culture
SAB2100378
Anti-CDC2 (ab1) antibody produced in rabbit, affinity isolated antibody
SAB2100379
Anti-CDC2 (ab2) antibody produced in rabbit, affinity isolated antibody
SAB2103891
Anti-CDC2 antibody produced in rabbit, affinity isolated antibody
SAB4500051
Anti-CDC2 antibody produced in rabbit, affinity isolated antibody
SAB4503707
Anti-CDC2 antibody produced in rabbit, affinity isolated antibody
HPA003387
Anti-CDK1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
PLA0045
Goat anti-ATM Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.
EHU089521 MISSION® esiRNA, esiRNA human ATM (esiRNA1)
SAB1402696
Monoclonal Anti-ATM antibody produced in mouse, clone 2C10, purified immunoglobulin, buffered aqueous solution
A1106
Monoclonal Anti-ATM antibody produced in mouse, ~2 mg/mL, clone MAT3-4G10/8, purified immunoglobulin, PBS solution
WH0000983M1
Monoclonal Anti-CDC2 antibody produced in mouse, clone 1A4-1A9, purified immunoglobulin, buffered aqueous solution
SAB1400047
Monoclonal Anti-CDC2 antibody produced in mouse, clone 1C7, purified immunoglobulin, buffered aqueous solution
PHR1098
N-Acetyl-L-cysteine, Pharmaceutical Secondary Standard; Certified Reference Material
C5H9NO3S
PLA0086
Rabbit anti-ATM Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.
PLA0287
Rabbit anti-CDK1 Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.