Demethoxycurcumin induces the apoptosis of human lung cancer NCI-H460 cells through the mitochondrial-dependent pathway

Abstract

Abstract. Lung cancer is the most common cause of cancerrelated mortality in the US as well as other regions of the world. Curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are the major components of Curcuma longa L. It has been reported that curcumin inhibits the growth of various types of cancer cells in vitro and in vivo. However, the mechanisms involved in the inhibition of cell growth and induced apoptosis by DMC in human lung cancer cells remain unclear. In the present study, we investigated the effect of DMC on cell death via the induction of apoptosis in NCI-H460 human lung cancer cells. Flow cytometric assay was used to examine the total percentage of viable cells, the population of cells in the sub-G1 phase of the cell cycle, the level of reactive oxygen species (ROS), Ca 2+ production, mitochondrial membrane potential (ΔΨm) and caspase activity. Western blotting was used to examine the changes in the expression of cell cycle-and apoptosis-associated proteins. Confocal microscopy was used to examine the translocation of apoptosis-associated proteins. The results indicated that DMC significantly induced cell morphological changes and decreased the percentage of viable NCI-H460 cells and DMC induced apoptosis based on the cell distribution in the sub-G1 phase. Moreover, DMC promoted ROS and Ca 2+ production and decreased the level of ΔΨm and promoted the activities of caspase-3, -8 and -9. The Western blotting results showed that DMC promoted the expression of AIF, Endo G and PARP. The levels of Fas ligand (Fas L) and Fas were also upregulated. Furthermore, DMC promoted expression of ER stress-associated proteins such as GRP78, GADD153, IRE1β, ATF-6α, ATF-6β and caspase-4. Based on the findings, we suggest that DMC may be used as a novel anticancer agent for the treatment of lung cancer in the future.

Curcuminoids combined with gefitinib mediated apoptosis and autophagy of human oral cancer SAS cells in vitro and reduced tumor of SAS cell xenograft mice in vivo

“…DMC induced G 2 /M cell cycle arrest and epigenetic changes in leukemia cells . Our previous study also showed that DMC induced the apoptosis of human lung cancer NCI‐H460 cells through the mitochondrial‐dependent pathway . BDMC inhibited adipogenesis in 3T3‐L1 preadipocytes and it had the potential to prevent obesity and induced cell apoptosis in human laryngeal carcinoma cells, activated hepatic stellate cells, and lung cancer NCI‐H460 cells .…”

Demethoxycurcumin: A naturally occurring curcumin analogue with antitumor properties

“…Therefore, novel treatment approaches for SCC are desperately needed. In an early study, Wu, Zhang, Yang, Ge, and Xin (2017) Ko, Lien, et al (2015) found that NCI-H460 cells treated with DMC were arrested in the S phase. Several studies have shown that cell death can be induced by increasing the expression of FAS/CD95 (Kumar, 2007;Wilson, 1998;Xu & Shi, 2007).…”

“…Several studies have shown that cell death can be induced by increasing the expression of FAS/CD95 (Kumar, 2007;Wilson, 1998;Xu & Shi, 2007). Ko, Lien, et al (2015) reported that in NCI-H460 cells treated with DMC, the level of FAS/ CD95 increased, which was accompanied by an increase in caspase-8…”

“…Furthermore, treatment of A431 and HaCaT cell lines with DMC resulted in cell-cycle arrest at the G2/M phase.3 | THE MECHANISMS UNDERLYING ANTICANCER EFFECTS OF DMC3.1 | DMC, apoptosis, and cell-cycle arrestMuch evidence has shown(Figure 1)that the stimulation or induction of apoptosis in cancer cells is one of the numerous treatment strategies for cancer patients. In an in vitro study on NCI-H460 cells byKo, Lien, et al (2015), it was shown that DCM induced changes in cellular morphology and reduced the percentage of live cells in a dose-dependent manner by inducing apoptosis and cell-cycle arrest.…”

Catan-ionic hybrid lipidic nano-carriers for enhanced bioavailability and anti-tumor efficacy of chemodrugs

“…It is necessary to create novel, efficacious and harmless treatment methods. Curcumin (CUR), a polyphenol extracted from the herb turmeric, shows cytotoxicity in three main kinds of NSCLCs: adenocarcinoma [ 4 ], squamous [ 5 ] and large-cell cancers [ 6 ]. Furthermore, CUR shows no effects on normal cells or animal models tested at a high dose of up to 10 g per day [ 7 ].…”