Archives of Toxicology

, Volume 87, Issue 12, pp 2141–2150 | Cite as

Effect of caffeic acid on Ca2+ homeostasis and apoptosis in SCM1 human gastric cancer cells

  • Hong-Tai Chang
  • I-Li Chen
  • Chiang-Ting Chou
  • Wei-Zhe Liang
  • Daih-Huang Kuo
  • Pochuen Shieh
  • Chung-Ren Jan
Molecular Toxicology


Caffeic acid is a natural phenolic compound that affects cellular Ca2+ homeostasis and viability in different cells. This study examined the effect of caffeic acid on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability in SCM1 human gastric cancer cells. The Ca2+-sensitive fluorescent dye fura-2 was used to measure [Ca2+]i. Caffeic acid-evoked [Ca2+]i rises concentration dependently. The response was reduced by removing extracellular Ca2+. Caffeic acid-evoked Ca2+ entry was inhibited by store-operated channel inhibitors (nifedipine, econazole, and SK&F96365) and protein kinase C activator (phorbol 12-myristate 13 acetate, PMA), but not by protein kinase C inhibitor (GF109203X). In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished caffeic acid-evoked [Ca2+]i rise. Conversely, treatment with caffeic acid decreased thapsigargin or BHQ-evoked [Ca2+]i rise. Inhibition of phospholipase C with U73122 abolished caffeic acid-evoked [Ca2+]i rise. At 200–800 μM, caffeic acid inhibited cell viability, which was not changed by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Caffeic acid between 400 and 800 μM also induced apoptosis. Collectively, in SCM1 cells, caffeic acid-induced [Ca2+]i rises by evoking phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via store-operated Ca2+ channels. Caffeic acid also caused Ca2+-independent apoptosis.


Caffeic acid Ca2+ Gastric cancer cells Apoptosis 


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Hong-Tai Chang
    • 1
    • 2
  • I-Li Chen
    • 3
  • Chiang-Ting Chou
    • 4
    • 5
  • Wei-Zhe Liang
    • 6
  • Daih-Huang Kuo
    • 3
  • Pochuen Shieh
    • 3
  • Chung-Ren Jan
    • 6
  1. 1.Department of SurgeryKaohsiung Veterans General HospitalKaohsiungTaiwan
  2. 2.College of ManagementNational Sun Yat-sen UniversityKaohsiungTaiwan
  3. 3.Department of PharmacyTajen UniversityPingtungTaiwan
  4. 4.Department of Nursing, Division of Basic Medical SciencesChang Gung University of Science and TechnologyChia-YiTaiwan
  5. 5.Chronic Diseases and Health Promotion Research CenterChang Gung University of Science and TechnologyChia-YiTaiwan
  6. 6.Department of Medical Education and ResearchKaohsiung Veterans General HospitalKaohsiungTaiwan

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