Glycitein induces reactive oxygen species-dependent apoptosis and G0/G1 cell cycle arrest through the MAPK/STAT3/NF-κB pathway in human gastric cancer cells.

Abstract

Glycitein is an isoflavone that reportedly inhibits the proliferation of human breast cancer and prostate cancer cells. However, its anti-cancer molecular mechanisms in human gastric cancer remain to be defined. This study evaluated the antitumor effects of glycitein on human gastric cancer cells and investigated the underlying mechanisms. We used MTT assay, flow cytometry and western blotting to investigate its molecular mechanisms with focus on reactive oxygen species (ROS) production. Our results showed that glycitein had significant cytotoxic effects on human gastric cancer cells. Glycitein markedly decreased mitochondrial transmembrane potential (ΔΨm) and increased AGS cells mitochondrial-related apoptosis, and caused G0/G1 cell cycle arrest by regulating cycle-related protein. Mechanistically, accompanying ROS, glycitein can activate mitogen-activated protein kinase (MAPK) and inhibited the signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappaB (NF-κB) signaling pathways. Furthermore, the MAPK signaling pathway regulated the expression levels of STAT3 and NF-κB upon treatment with MAPK inhibitor and N-acetyl-L-cysteine (NAC). These findings suggested that glycitein induced AGS cell apoptosis and G0/G1 phase cell cycle arrest via ROS-related MAPK/STAT3/NF-κB signaling pathways. Thus, glycitein has the potential to a novel targeted therapeutic agent for human gastric cancer.

• Authors: Yan-Qing Zang, Yan-Yu Feng, Ying-Hua Luo, Yu-Qing Zhai, Xue-Ying Ju, Yu-Chao Feng, Jia-Ru Wang, Chang-Qing Yu, Cheng-Hao Jin
• Journal: Drug development research (Drug Dev Res) Vol. 80 Issue 5 Pg. 573-584 (08 2019) ISSN: 1098-2299 [Electronic] United States
• PMID: 30916421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents, Phytogenic
• Isoflavones
• NF-kappa B
• Reactive Oxygen Species
• STAT3 Transcription Factor
• STAT3 protein, human
• glycitein
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Cell Cycle Checkpoints
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Humans
• Isoflavones (pharmacology)
• MAP Kinase Signaling System (drug effects)
• Membrane Potential, Mitochondrial (drug effects)
• NF-kappa B (metabolism)
• Reactive Oxygen Species (metabolism)
• STAT3 Transcription Factor (metabolism)
• Stomach Neoplasms (drug therapy, metabolism)