Effect of diindolylmethane on Ca 2+ movement and viability in HA59T human hepatoma cells

Jin Shiung Cheng, Su Shung Shu, Chun Chi Kuo, Chiang Ting Chou, Wei Lun Tsai, Yi Chien Fang, Li Ni Kuo, Jeng Hsien Yeh, Wei Chuan Chen, Jau Min Chien, Ti Lu, Chih Chuan Pan, He Hsiung Cheng, Kuo Liang Chai, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

17 Scopus citations


The effect of diindolylmethane, a natural compound derived from indole-3-carbinol in cruciferous vegetables, on cytosolic Ca 2+ concentrations ([Ca 2+] i) and viability in HA59T human hepatoma cells is unclear. This study explored whether diindolylmethane changed [Ca 2+] i in HA59T cells. The Ca 2+-sensitive fluorescent dye fura-2 was applied to measure [Ca 2+] i. Diindolylmethane at concentrations of 1-50 μM evoked a [Ca 2+] i rise in a concentration-dependent manner. The signal was reduced by removing Ca 2+. Diindolylmethane-induced Ca 2+ influx was not inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators but was inhibited by aristolochic acid. In Ca 2+-free medium, treatment with the endoplasmic reticulum Ca 2+ pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished diindolylmethane-induced [Ca 2+] i rise. Incubation with diindolylmethane inhibited thapsigargin or BHQ-induced [Ca 2+] i rise. Inhibition of phospholipase C with U73122 reduced diindolylmethane-induced [Ca 2+] i rise. At concentrations of 10-75 μM, diindolylmethane killed cells in a concentration-dependent manner. The cytotoxic effect of diindolylmethane was not reversed by chelating cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N′, N′-tetraacetic acid. Propidium iodide staining data suggest that diindolylmethane (25-50 μM) induced apoptosis in a concentration-dependent manner. Collectively, in HA59T cells, diindolylmethane induced a [Ca 2+] i rise by causing phospholipase C-dependent Ca 2+ release from the endoplasmic reticulum and Ca 2+ influx via phospholipase A 2-sensitive channels. Diindolylmethane induced cell death that may involve apoptosis.

Original languageEnglish
Pages (from-to)1257-1266
Number of pages10
JournalArchives of Toxicology
Issue number10
StatePublished - 10 2011
Externally publishedYes


  • Ca
  • Diindolylmethane
  • HA59T
  • Hepatoma


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