Curcumin is the main active ingredient extracted from the traditional Chinese medicine, turmeric, which acts against non-small cell lung cancer cell (NSCLC), lowers blood pressure, is anti-inflammatory, choleretic, and exerts anti‑oxidant effects, without any obvious toxicity in the long term. The aim of the present study was to investigate whether the anticancer effect of curcumin inhibited cell proliferation and induced apoptosis of human NSCLC through the upregulation of microRNA‑192-5p (miR-192-5p) and suppression of the PI3K/Akt signaling pathway. In the present study, treatment with curcumin inhibited cell proliferation, induced cell apoptosis and increased the caspase-3 activity of A549 cells. The results also showed that, miR-192-5p relative expression of NCL-H460 cells was relatively lower than that of A549 cells, which was higher, with that of BEAS-2E cells being the highest. miR-192-5p mimics suppressed cell proliferation and increased cell apoptosis of A549 cells. However, anti-miR-192-5p mimics increased cell proliferation and inhibited cell apoptosis of A549 cells. Curcumin treatment effectively increased the relative miR‑192-5p expression and suppressed the PI3K/Akt signaling pathway. miR-192-5p mimics enhanced the effect of curcumin on cell viability and apoptosis and suppressed the PI3K/Akt signaling pathway in A549 cells. Anti-miR-192-5p mimics reversed the effect of curcumin on A549 cells and PI3K/Akt expression. Collectively, our findings suggested that curcumin inhibited cell proliferation and induced apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of the PI3K/Akt signaling pathway.

Heart remodeling is associated with the loss of cardiomyocytes and increase of fibrous tissue owing to abnormal mechanical load in a number of heart disease conditions. In present study, a well-described in vitro sustained stretch model was employed to study mechanical stretch-induced responses in both neonatal cardiomyocytes and cardiac fibroblasts. Cardiomyocytes, but not cardiac fibroblasts, underwent mitochondria-dependent apoptosis as evidenced by cytochrome c (cyto c) and Smac/DIABLO release from mitochondria into cytosol accompanied by mitochondrial membrane potential (∆ψ m ) reduction, indicative of mitochondrial permeability transition pore (PTP) opening. Cyclosporin A, an inhibitor of PTP, inhibited stretch-induced cyto c release, ∆ψ m reduction and apoptosis, suggesting an important role of mitochondrial PTP in stretch-induced apoptosis. The stretch also resulted in increased expression of the pro-apoptotic Bcl-2 family proteins, including Bax and Bad, in cardiomyocytes, but not in fibroblasts. Bax was accumulated in mitochondria following stretch. Cell permeable Bid-BH3 peptide could induce and facilitate stretch-induced apoptosis and ∆ψ m reduction in cardiomyocytes. These results suggest that Bcl-2 family proteins play an important role in coupling stretch signaling to mitochondrial death machinery, probably by targeting to PTP. Interestingly, the levels of p53 were increased at 12 h after stretch although we observed that Bax upregulation and apoptosis occurred as early as 1 h. Adenovirus delivered dominant negative p53 blocked Bax upregulation in cardiomyocytes but showed partial effect on preventing stretch-induced apoptosis, suggesting that p53 was only partially involved in mediating stretch-induced apoptosis. Furthermore, we showed that p21 was upregulated and cyclin B1 was downregulated only in cardiac fibroblasts, which may be associated with G 2 /M accumulation in response to mechanical stretch.

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Myostatin, a member of the transforming growth factor-β superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induced significant mitochondrial metabolic alterations and prolonged exposure of myostatin induced mitochondria-dependent apoptosis in cancer cells addicted to glycolysis. To address the underlying mechanism, we found that the protein levels of Hexokinase II (HKII) and voltage-dependent anion channel 1 (VDAC1), two key regulators of glucose metabolisms as well as metabolic stress-induced apoptosis, were negatively correlated. In particular, VDAC1 was dramatically upregulated in cells that are sensitive to myostatin treatment whereas HKII was downregulated and dissociated from mitochondria. Myostatin promoted the translocation of Bax from cytosol to mitochondria, and knockdown of VDAC1 inhibited myostatin-induced Bax translocation and apoptosis. These apoptotic changes can be partially rescued by repletion of ATP, or by ectopic expression of HKII, suggesting that perturbation of mitochondrial metabolism is causally linked with subsequent apoptosis. Our findings reveal novel function of myostatin in regulating mitochondrial metabolism and apoptosis in cancer cells.

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The present study investigates the molecular details of how arsenic trioxide inhibits preadipocyte differentiation and examines the role of Akt/PKB in regulation of differentiation and apoptosis. Continual exposure of arsenic trioxide, at the clinic achievable dosage that does not induce apoptosis, suppressed 3T3-L1 cell differentiation into fat cells by inhibiting the expression of PPARγ and C/EBPα and disrupting the interaction between PPARγ and RXRα, which determines the programming of the adipogenic genes. Interestingly, if we treated the cells for 12 or 24 h and then withdrew arsenic trioxide, the cells were able to differentiate to the comparable levels of untreated cells as assayed by the activity of GAPDH, the biochemical marker of preadipocyte differentiation. Long term treatment blocked the differentiation and the activity of GAPDH could not recover to the comparable levels of untreated cells. Continual exposure of arsenic trioxide caused accumulation in G2/M phase and the accumulation of p21. We found that arsenic trioxide induced the expression and the phosphorylation of Akt/PKB and it inhibited the interaction between Akt/PKB and PPARγ . Akt/PKB inhibitor appears to block the arsenic trioxide suppression of differentiation. Our results suggested that Akt/PKB may play a role in suppression of apoptosis and negatively regulate preadipocyte differentiation.

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