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.
Bibliographical noteFunding Information:
This work was supported by Grants NSC-94-2745-B-039-002-URD and NSC 95-2745-B-039-002-URD from the National Science Council of Taiwan.
- Cell cycle arrest
- Mitochondrial membrane potential (ΔΨ)
- Reactive oxygen species (ROS)