LZ-207, a Newly Synthesized Flavonoid, Induces Apoptosis and Suppresses Inflammation-Related Colon Cancer by Inhibiting the NF-κB Signaling Pathway.

Abstract

Flavonoids and flavonoid derivatives, which have significant biological and pharmacological activities, including antitumor and anti-inflammatory activities, have been widely used in human healthcare. To design a more effective flavonoid antitumor agent, we altered the flavonoid backbone with substitutions of piperazine and methoxy groups to synthesize a novel flavonoid derivative, LZ-207. The anticancer effect of LZ-207 against HCT116 colon cancer cells and the underlying mechanism of this effect were explored in this study. Specifically, LZ-207 exhibited inhibitory effects on growth and viability in several human colon cancer cell lines and induced apoptosis in HCT116 cells both in vitro and in vivo. LZ-207 treatment also suppressed the nuclear translocation of NF-κB and the phosphorylation of IκB and IKKα/β in a dose-dependent manner in both HCT116 cells and human acute monocytic leukemia THP-1 cells. Moreover, LZ-207 also reduced the secretion of the pro-inflammatory cytokine interleukin-6 (IL-6) in LPS-induced THP-1 cells, and this effect was confirmed at the transcriptional level. Furthermore, LZ-207 significantly inhibited HCT116 cell proliferation that was elicited by LPS-induced THP-1 cells in a co-culture system. These findings elucidated some potential molecular mechanisms for preventing inflammation-driven colon cancer using the newly synthesized flavonoid LZ-207 and suggested the possibility of further developing novel therapeutic agents derived from flavonoids.

• Authors: Jie Sun, Fanni Li, Yue Zhao, Li Zhao, Chen Qiao, Zhiyu Li, Qinglong Guo, Na Lu
• Journal: PloS one (PLoS One) Vol. 10 Issue 5 Pg. e0127282 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26023926 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Flavones
• Flavonoids
• LZ-207
• NF-kappa B
• Piperazines

Topics

• Apoptosis (drug effects)
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Flavones (chemistry, pharmacology, therapeutic use)
• Flavonoids (chemistry, pharmacology, therapeutic use)
• HCT116 Cells
• HT29 Cells
• Human Umbilical Vein Endothelial Cells
• Humans
• NF-kappa B (metabolism)
• Piperazines (chemistry, pharmacology, therapeutic use)
• Signal Transduction (drug effects)
• Xenograft Model Antitumor Assays