DNA damage and endoplasmic reticulum stress mediated curcumin-induced cell cycle arrest and apoptosis in human lung carcinoma A-549 cells through the activation caspases cascade- and mitochondrial-dependent pathway

Song Shei Lin, Hsuan Pang Huang, Jai Sing Yang, Jeng Yuan Wu, Te Chun Hsai, Chin Chung Lin, Cheng Wen Lin, Chao Lin Kuo, W. Gibson Wood, Jing Gung Chung

Research output: Contribution to journalArticle

144 Scopus citations

Abstract

Curcumin, a major component of the Curcuma species, is known to have antioxidant, anti-inflammatory properties and induce apoptosis of cancer cells, however, the precise molecular mechanisms of apoptosis in vitro are unclear. In this study, we showed that curcumin, a plant product containing the phenolic phytochemical, caused DNA damage and endoplasmic reticulum (ER) stress and mitochondrial-dependent-induced apoptosis through the activation of caspase-3 at a treatment concentration of 30 μM in human lung cancer A-549 cells. In contrast, treatment with 5-10 μM of curcumin did not induce significant apoptosis, but rather induced G2/M-phase arrest in A-549 cells. Flow cytometric analysis indicated that curcumin directly increased intracellular oxidative stress based on the cell permeable dye, 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) acting as an indicator of reactive oxygen species (ROS) generation. GADD153 and GRP78 were increased by curcumin which was indicative of ER stress. Curcumin increased Ca2+ levels and the mitochondrial membrane potential (ΔΨm), was decreased in A-549 cells. Overall, our results demonstrated that curcumin treatment causes cell death by activating pathways inducing G2/M-phase arrest and apoptosis.

Original languageEnglish (US)
Pages (from-to)77-90
Number of pages14
JournalCancer Letters
Volume272
Issue number1
DOIs
StatePublished - Dec 8 2008

Keywords

  • Apoptosis
  • Ca
  • Caspase-3
  • Cell cycle arrest
  • Curcumin
  • Mitochondrial membrane potential (ΔΨ)
  • Reactive oxygen species (ROS)

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