Novel derivative of benzofuran induces cell death mostly by G2/M cell cycle arrest through p53-dependent pathway but partially by inhibition of NF-κB

Sunil K. Manna, Julie S. Bose, Vijay Gangan, Nune Raviprakash, Thota Navaneetha, Pongali B. Raghavendra, Banaganapalli Babajan, Chitta S. Kumar, Swatantra K. Jain

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Abstract

The Dracaena resin is widely used in traditional medicine as an anticancer agent, and benzofuran lignan is the active component. In this report, we provide evidence that the synthetic derivative of benzofuran lignan (Benfur) showed antitumor activities. It induced apoptosis in p53-positive cells. Though it inhibited endotoxin-induced nuclear factor κB (NF-κB) activation in both p53-positive and -negative cells, the activation of caspase 3 was observed in p53-positive cells. It showed partial cell death effect in both p53-positive and -negative cells through inhibition of NF-κB. Cell cycle analysis using flow cytometry showed that treatment with this novel benozofuran lignan derivative to Jurkat T-cells, but not U-937 cells, resulted in a G2/M arrest in a dose- and time-dependent manner. It increased amounts of p21, p27, and cyclin B, but not phospho-Rb through p53 nuclear translocation in Jurkat T-cells, but not in U-937 cells. It inhibited amounts ofMDM2(murine double minute 2) by repressing the transcription factor Sp1, which was also proved in silico. It induced cell death in tumor cells, but not in primary T-cells. Overall, our data suggest that Benfurmediated cell death is partially dependent upon NF-κB, but predominantly dependent on p53. Thus, this novel benzofuran lignan derivative can be effective chemopreventive or chemotherapeutic agent against malignant T-cells.

Original languageEnglish
Pages (from-to)22318-22327
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number29
DOIs
Publication statusPublished - 16-07-2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Manna, S. K., Bose, J. S., Gangan, V., Raviprakash, N., Navaneetha, T., Raghavendra, P. B., Babajan, B., Kumar, C. S., & Jain, S. K. (2010). Novel derivative of benzofuran induces cell death mostly by G2/M cell cycle arrest through p53-dependent pathway but partially by inhibition of NF-κB. Journal of Biological Chemistry, 285(29), 22318-22327. https://doi.org/10.1074/jbc.M110.131797