Curcumin induces autophagy via activating the AMPK signaling pathway in lung adenocarcinoma cells.

Curcumin is a major yellow pigment and active component of turmeric widely used as dietary spice and herbal medicine. This compound has been reported to be a promising antitumor agent, although the underlying molecular mechanisms are not fully understood yet. In this study, we reported that curcumin inhibited growth of lung adenocarcinoma cells, but had no cytotoxic activity to IMR-90 normal lung fibroblast cells. Curcumin induced autophagy in the A549 human lung adenocarcinoma cell line, evidenced by LC3 immunofluorescence analysis and immunoblotting assays on LC3 and SQSTM1. Moreover, the autophagy inhibitor 3-MA partly blocked the inhibitory effect of curcumin on the growth of A549 cells. Curcumin markedly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetylCoA carboxylase in A549 cells. At last, pharmacological blockade of the AMPK signaling pathway by compound C and genetic disruption of the AMPK signaling pathway with siRNA-mediated AMPKα1 knockdown impaired the autophagy-inducing effect of curcumin. Collectively, our data suggests that curcumin induces autophagy via activating the AMPK signaling pathway and the autophagy is important for the inhibiting effect of curcumin in lung adenocarcinoma cells.

Safe temperature range for intraoperative and early postoperative continuous hyperthermic intraperitoneal perfusion in a swine model of experimental distal gastrectomy with Billroth II reconstruction.

BACKGROUND: The current study sought to investigate the safety of intraoperative and early postoperative continuous hyperthermic intraperitoneal perfusion (IEPCHIP) at different temperatures in a swine model of experimental distal gastrectomy with Billroth II reconstruction. METHODS: Thirty pigs were randomly divided into 5 groups. Two groups were used as the control groups (groups A1 and A2), and 3 groups were used as the perfusion groups (groups B, C and D). Pigs in group A1 received distal gastrectomy with Billroth II reconstruction only. Pigs in groups A2, B, C and D received the same surgery as group A1, followed by IEPCHIP at 37 ± 0.5°C, 42.5 ± 0.5°C, 43.5 ± 0.5°C or 44.5 ± 0.5°C, respectively. The perfusion time was assessed for each pig in group A2 as well as in the perfusion groups, and the perfusions were performed twice for each group. The first perfusion was conducted intraoperatively, and the second perfusion was initiated 1 day after surgery. Data concerning vital signs and hepatic and renal function were collected. Parameters concerning anastomotic healing, the pathology of the anastomotic tissue and abdominal adhesion were compared. RESULTS: The vital signs and hepatic and renal functions of the pigs in groups A1, A2, B and C were not significantly affected by this procedure. In contrast, the vital signs and hepatic and renal functions of the pigs in group D were significantly affected. Compared to the pigs in groups A1, A2 or B, the anastomotic bursting pressure, breaking strength and hydroxyproline content in group C and D pigs were significantly lower. No significant differences were observed in these parameters between groups A1, A2 and B. Abdominal adhesion was more severe in group D pigs. Collagen deposition in group A1, A2 and B pigs was dense in the anastomosis, and inflammatory cell infiltration was observed in group D. CONCLUSIONS: IEPCHIP at 42.5 ± 0.5°C was safe and caused minimal impairments. However, anastomotic healing was affected by perfusion at 43.5 ± 0.5°C and 44.5 ± 0.5°C, and abdominal adhesion was most severe in the group D animals, which were perfused at 44.5 ± 0.5°C.

Preventive effects of curcumin and dexamethasone on lung transplantation-associated lung injury in rats.

OBJECTIVE: To investigate potential effects of curcumin or dexamethasone on lung transplantation-associated lung injury. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Sham-operated rats were used as time-matched controls. Experimental rats were subjected to unilateral orthotopic lung transplantation with 4 hrs of cold ischemia followed by 2 hrs (or 24 hrs) of reperfusion. Animals were randomly assigned to vehicle-, curcumin-, or dexamethasone-treated groups. MEASUREMENTS AND MAIN RESULTS: Transplantation-associated lung injury was characterized by an increased alveolar-capillary permeability and myeloperoxidase activity and decreased levels of arterial oxygen tension/inspired oxygen concentration ratio. Pretreatment with curcumin and dexamethasone significantly prevented barrier disruption, lung edema, tissue inflammation, and decreased PaO2 at the early stage of posttransplantation. Nuclear factor-kappaB in transplanted lungs was activated, accompanied by an increase in messenger RNA levels and protein content of tumor necrosis factor-alpha, interleukin-6, and matrix metalloproteinase-9 in lung graft. Those changes were prevented by pretreatment with curcumin and dexamethasone. CONCLUSIONS: Curcumin can be an alternative therapy for protecting lung transplantation-associated injury by suppressing nuclear factor-kappaB-mediated expression of inflammatory genes.