Effects of thymol on Ca 2+ homeostasis and apoptosis in MDCK renal tubular cells

Hong Tai Chang, Chiang Ting Chou, Wei Zhe Liang, Ti Lu, Daih Huang Kuo, Pochuen Shieh, Chin Man Ho, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

13 Scopus citations


Thymol is a natural essential oil present in many plants and has many different effects in various cell types. However, the effect of thymol on the physiology of Madin-Darby canine kidney (MDCK) renal tubular cells is unknown. The action of the phytochemical thymol on cytosolic Ca 2+ concentrations ([Ca 2+ ]i) and apoptosis in MDCK renal tubular cells was explored. Fura-2, a Ca 2+ -sensitive fluorescent dye, was used to assess [Ca 2+ i. Thymol at concentrations of 200-500 μM caused a [Ca 2+ ]i rise in a concentration-dependent manner. Removal of extracellular Ca 2+ partially reduced the effects of thymol. Thymol-induced Ca 2+ entry was inhibited by nifedipine, econazole, SK&F96365 and protein kinase C modulators. In a Ca 2+ -free medium, treatment with the endoplasmic reticulum Ca 2+ pump inhibitor thapsigargin inhibited thymol-induced [Ca 2+ ]i increases. Treatment with thymol also inhibited thapsigargin-induced [Ca 2+ i rise. Thymol killed cells at concentrations of 300-500 μM in a concentrationdependent fashion. Chelating cytosolic Ca 2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM) did not prevent thymol cytotoxicity. Thymol (400 and 500 μM) induced apoptosis detected by using Annexin V/propidium iodide staining. At 400 or 500 μM, thymol increased levels of reactive oxygen species (ROS). Together, in MDCK cells, thymol induced a [Ca 2+ ]i rise by inducing Ca 2+ release from the endoplasmic reticulum and Ca 2+ entry via protein kinase C-sensitive store-operated Ca 2+ channels. Our data suggest that thymol-induced apoptosis might involve ROS production.

Original languageEnglish
Pages (from-to)90-98
Number of pages9
JournalChinese Journal of Physiology
Issue number2
StatePublished - 2014
Externally publishedYes


  • Apoptosis
  • MDCK
  • Thymol


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