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  • Title: Curcumin induces apoptosis through FAS and FADD, in caspase-3-dependent and -independent pathways in the N18 mouse-rat hybrid retina ganglion cells.
    Author: Lu HF, Lai KC, Hsu SC, Lin HJ, Yang MD, Chen YL, Fan MJ, Yang JS, Cheng PY, Kuo CL, Chung JG.
    Journal: Oncol Rep; 2009 Jul; 22(1):97-104. PubMed ID: 19513510.
    Abstract:
    Curcumin, a naturally occurring yellow pigment isolated from turmeric, is a well known antioxidant with broad spectrum of anti-tumor activities against many human cancer cells. In this study, curcumin-induced cytotoxic effect of mouse-rat hybrid retina ganglion cells (N18) were investigated. For determining cell viability, the trypan blue exclusion and flow cytometric analysis were used. The curcumin-caused cell cycle arrest in N18 cells was examined by flow cytometry. Curcumin affect on the production of reactive oxygen species and Ca2+ and on the decrease of the level of mitochondria membrane potential (DeltaPsim) were also examined by flow cytometry. Curcumin-induced apoptosis was determined by DAPI staining and Western blotting was used for examining the apoptotic signaling proteins. Cell cycle analysis showed that G2/M phase arrest and sub-G1 occurs in N18 cells following 48 h exposure to curcumin. Curcumin also caused a marked increase in apoptosis, as characterized by DNA fragmentation (sub-G1 phase formation) and DAPI staining, and dysfunction of mitochondria, which was associated with the activation of caspase-8, -9 and -3. Curcumin also promoted the levels of Fas and FADD, Bax, cytochrome c release, but decreased the levels of Bcl-2 causing changes of DeltaPsim. Curcumin also induced endoplasmic reticulum stress in N18 cells which was based on the changes of GADD153 and GRP78 and caused Ca2+ release. Curcumin induced apoptosis through the intrinsic pathway and caspase-3-dependent and -independent pathways in N18 cells.
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