Curcumin induces apoptosis in human lung adenocarcinoma A549 cells through a reactive oxygen species-dependent mitochondrial signaling pathway

Abstract

Abstract.Several studies have shown that curcumin can induce apoptosis and inhibit growth in human A549 lung adenocarcinoma cells. However, the mechanism is not completely understood yet. The present study was designed to investigate the effects of curcumin on A549 cells to better understand its apoptosis and apoptosis-related factors in vitro. The apoptosis induction, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were examined by confocal fluorescence microscope and flow cytometry. The MAPK protein expression was examined by Western blot analysis. After treatment with curcumin, apoptosis were observed. Curcumin-induced apoptosis was accompanied by an increase of intracellular ROS level and a loss of MMP. In addition, induction of apoptosis was also accompanied by sustained phosphorylation and activation of JNK, p38 and ERK. However, pretreatment with MAPK inhibitors had no effect upon curcumin-induced apoptosis. GSH and NAC, an anti-oxidant agent, blocked the curcumin-induced ROS production, MMP loss and rescued cells from curcumininduced apoptosis. Our results indicated that curcumin induced apoptosis in A549 cells through a reactive oxygen speciesdependent mitochondrial signaling pathway and independent of MAPK signaling pathway.

Carboplatin resistant human laryngeal carcinoma cells are cross resistant to curcumin due to reduced curcumin accumulation

“…There are numerous reports about the production of reactive oxygen species (ROS) as one of the first steps in curcumin cytotoxicity to different tumor cell lines (Atsumi et al, 2005;Chen et al, 2010;Fujisawa S, 2004;Hail, 2008;Kang et al, 2005). We also detected ROS formation quite early after curcumin was added and found more ROS in parental HEp-2 cells.…”

“…There are numerous reports about ROS involvement in curcumin induced apoptosis in the literature (Atsumi et al, 2005;Chen et al, 2010;Fujisawa S, 2004;Hail, 2008;Kang et al, 2005). Apoptosis inhibition was found to be one of the causes of resistance to curcumin in some cell lines (Karunagaran et al, 2005).…”

“…Numerous literature data suggest that ROS induction is one of the first effects of curcumin treatment and it is involved in its cytotoxicity (Chen et al, 2010;Fujisawa S, 2004;Khar et al, 2001). Therefore, we examined and compared ROS induction in HEp-2 and 7T cells following the treatment with curcumin.…”

“…There are numerous reports about the production of reactive oxygen species (ROS) during curcumin-induced apoptosis in different tumor cell lines (Atsumi et al, 2005;Chen et al, 2010;Fujisawa S, 2004;Hail, 2008;Kang et al, 2005). These free radicals can cause serious damage to lipids, proteins, and DNA (Halliwell and Gutteridge, 1999) and they have been suggested as some of the initiators in apoptotic signaling (Carmody and Cotter, 2001;Circu and Aw, 2010).…”

Curcumin inhibits proliferation of human lens epithelial cells: a proteomic analysis

“…Cur has been shown to enhance monokaryon phagocytosis by macrophages, increase immune regulation, inhibit the proliferation, and induce apoptosis of immortal cell lines such as HL-60, K-562, MCF-7, HOS, and VSM cells (Dubey et al, 2008;Hussain et al, 2008;Miller et al, 2008;Lee et al, 2009;Chen et al, 2010a;2010b;Giommarelli et al, 2010;Watson et al, 2010). In our previous studies, we found that Cur effectively inhibited LEC proliferation, and that Cur increased the concentrations of intracellular Ca 2+ and cyclic adenosine monophosphate and decreased the concentration of cyclic guanosine monophosphate in LECs (Hu et al, 2006a;2006b).…”