The p38 MAPK pathway is critical for 5,5′-dibromodiindolylmethane- induced apoptosis to prevent oral squamous carcinoma cells

Kyeong Hee Choi, Hyung Kook Kim, Jun Hee Kim, Eun Sun Choi, Ji Ae Shin, Syng Ook Lee, Sudhakar Chintharlapalli, Stephen Safe, Maen Abdelrahim, Gu Kong, Hong Seok Choi, Ji Youn Jung, Hyun Tae Cho, Nam Pyo Cho, Sung Dae Cho

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Cruciferous vegetables contain isothiocyanates including diindolylmethane (DIM) that exhibit cancer chemopreventive effects. We developed a series of synthetic ring-substituted DIM analogs including 5,5′-dibromoDIM that exhibited better inhibitory activity in breast and colon cancer cells than DIM. In this study, we investigated whether 5,5′-dibromoDIM inhibits the proliferation of KB and YD-10B oral squamous carcinoma cell lines. 5,5′-dibromoDIM decreased the cell survival and inhibited the growth of oral cancer cells. Exposure of KB and YD-10B cells to 5,5′-dibromoDIM induced caspase-dependent apoptosis evidenced by poly-ADP ribose polymerase cleavage, accumulation of sub-G1 population, and nuclear condensation and fragmentation. In addition, apoptotic cell death was correlated with damage to the mitochondrial membrane potential through a decrease in the level of Bcl-2 protein expression. Mechanistic studies showed that mitochondria-dependent apoptosis induced by 5,5′-dibromoDIM was mediated by the p38 mitogen-activated protein kinase pathway but not the ERK1/2 and JNK pathway. These results highlight 5,5′-dibromoDIM as an important chemopreventive agent for the clinical treatment of oral cancer through the p38 mitogen-activated protein kinase pathway.

Original languageEnglish (US)
Pages (from-to)153-159
Number of pages7
JournalEuropean Journal of Cancer Prevention
Volume19
Issue number2
DOIs
StatePublished - Mar 2010

Keywords

  • 5,5′-dibromodiindolylmethane
  • Apoptosis
  • Bcl-2
  • Human oral squamous carcinoma cells
  • Mitochondrial membrane potentials
  • P38 mitogen-activated protein kinase

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Public Health, Environmental and Occupational Health
  • Cancer Research

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