• Home
  • Search Results
  • Jaridonin-induced G2/M phase arrest in human esophageal cancer cells is caused by reactive oxygen species-dependent Cdc2-tyr15 phosphorylation via ATM-Chk1/2-Cdc25C pathway.

Jaridonin-induced G2/M phase arrest in human esophageal cancer cells is caused by reactive oxygen species-dependent Cdc2-tyr15 phosphorylation via ATM-Chk1/2-Cdc25C pathway.

Toxicology and applied pharmacology (2014-12-03)
Yong-Cheng Ma, Nan Su, Xiao-Jing Shi, Wen Zhao, Yu Ke, Xiaolin Zi, Ning-Min Zhao, Yu-Hua Qin, Hong-Wei Zhao, Hong-Min Liu
ABSTRACT

Jaridonin, a novel diterpenoid from Isodon rubescens, has been shown previously to inhibit proliferation of esophageal squamous cancer cells (ESCC) through G2/M phase cell cycle arrest. However, the involved mechanism is not fully understood. In this study, we found that the cell cycle arrest by Jaridonin was associated with the increased expression of phosphorylation of ATM at Ser1981 and Cdc2 at Tyr15. Jaridonin also resulted in enhanced phosphorylation of Cdc25C via the activation of checkpoint kinases Chk1 and Chk2, as well as in increased phospho-H2A.X (Ser139), which is known to be phosphorylated by ATM in response to DNA damage. Furthermore, Jaridonin-mediated alterations in cell cycle arrest were significantly attenuated in the presence of NAC, implicating the involvement of ROS in Jaridonin's effects. On the other hand, addition of ATM inhibitors reversed Jaridonin-related activation of ATM and Chk1/2 as well as phosphorylation of Cdc25C, Cdc2 and H2A.X and G2/M phase arrest. In conclusion, these findings identified that Jaridonin-induced cell cycle arrest in human esophageal cancer cells is associated with ROS-mediated activation of ATM-Chk1/2-Cdc25C pathway.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Glutathione reduced, ≥98.0%
Sigma-Aldrich
Caffeine, powder, ReagentPlus®
Sigma-Aldrich
N-Acetyl-L-cysteine, Sigma Grade, ≥99% (TLC), powder
Sigma-Aldrich
N-Acetyl-L-cysteine, BioReagent, suitable for cell culture
Sigma-Aldrich
Propidium iodide, ≥94.0% (HPLC)
Supelco
Caffeine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Propidium iodide solution, solution (1.0 mg/ml in water)
Sigma-Aldrich
L-Glutathione reduced, suitable for cell culture, BioReagent, ≥98.0%, powder
Sigma-Aldrich
Caffeine, anhydrous, 99%, FCC, FG
Supelco
Glutathione, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Caffeine, Sigma Reference Standard, vial of 250 mg
Sigma-Aldrich
L-Glutathione reduced, BioXtra, ≥98.0%
Supelco
Caffeine Melting Point Standard, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Melting point standard 235-237°C, analytical standard
Supelco
Caffeine, certified reference material, TraceCERT®
Sigma-Aldrich
N-Acetyl-L-cysteine, BioXtra, ≥99% (TLC)
Sigma-Aldrich
Propidium iodide, ≥94% (HPLC)
Supelco
N-Acetyl-L-cysteine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Dihydroethidium, ≥95%
USP
Acetylcysteine, United States Pharmacopeia (USP) Reference Standard
Supelco
Mettler-Toledo Calibration substance ME 18872, Caffeine, analytical standard, for the calibration of the thermosystem 900, traceable to primary standards (LGC)
Sigma-Aldrich
Caffeine, meets USP testing specifications, anhydrous
Glutathione, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Dihydroethidium, BioReagent, suitable for fluorescence, ≥95% (HPCE)
USP
Caffeine, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Caffeine, anhydrous, tested according to Ph. Eur.
Acetylcysteine, European Pharmacopoeia (EP) Reference Standard
USP
Caffeine melting point standard, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Caffeine, BioXtra
Caffeine, European Pharmacopoeia (EP) Reference Standard