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The high incidence of chronic obstructive pulmonary disease (COPD), one of the most prevalent diseases worldwide, has attracted growing attention. Cigarette smoking is considered a major contributory factor in the pathogenesis and progression of COPD due to the tremendous oxidative burden that it causes, which induces an oxidant/antioxidant imbalance. Excessive oxidation induced by the excessive generation of mitochondrial reactive oxygen species disturbs the antioxidant systems and plays an important role in triggering and promoting chronic inflammation of airways. Given that mitochondria is one of the main sites of reactive oxygen species production by the oxidative phosphorylation process, oxidative stress may affect mitochondrial function by changing its structure and morphology and by affecting a series of mitochondrial proteins. In particular, PTEN-induced putative kinase 1/Parkin and p62 play critical roles in mitophagy. During the process, the Akt ubiquitin E3 ligase is an important mediator associated with cigarette smoke exposure-induced pulmonary endothelial cell death and dysfunction. Thus, understanding the underlying mechanisms of the signaling pathway may provide important information regarding the therapeutic treatment of COPD by application of alternative PTEN-induced putative kinase 1 targets or ubiquitin E3 ligase.

Furanodienone, a major bioactive constituents of sesquiterpene derived from Rhizoma Curcumae, has been proven to possess the potent anticancer efficacy on human breast cancer cells. Here, we investigated the cytotoxicity of furanodienone on human colorectal carcinoma cell lines in vitro and in vivo, as well as its underlying molecular mechanisms in the induction of apoptosis. In this study, we found that furanodienone significantly inhibited proliferation of RKO and HT-29 cells, induced mitochondrial dysfunction characterized by collapse of mitochondrial transmembrane potential and reduction of ATP level, and promoted the production of reactive oxygen species (ROS) that functions upstream of caspase-dependent apoptosis. The antioxidant N-acetyl cysteine, a ROS scavenger, abolished this apoptosis induced by furanodienone. In addition, furanodienone elevated the expression of p-p38, p-JNK, but decreased p-ERK, as a result of the produced ROS. The specific inhibitors U0126, SP600125 and SB202190 attenuated the expression of MAPKs, and regulated the expression of cleaved caspase-8, -9 and -3. Furthermore, the potential inhibitory effect of furanodienone on CRC cells was also corroborated in mouse xenograft model. In conclusion, the results demonstrated that furanodienone-triggered ROS plays a pivotal role in apoptosis as an upstream molecule-modulating activity of caspases in mitochondrial pathway via stimulating MAPKs signaling pathway. Our finding may provide a novel candidate for development of antitumor drugs targeting on colorectal cancer.