ABSTRACT
Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990) with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153), a marker of the endoplasmic-reticulum-stress- (ERS-) mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78), phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK), and phosphoeukaryotic initiation factor-2 α (phospho-eIF2 α ), activating transcription factor 4 (ATF4) and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin.
ABSTRACT
Oxymatrine, the main alkaloid component in the traditional Chinese herbal medicine Sophora japonica (Sophora flavescens Ait), has been reported to have antitumor properties. However, the mechanisms of action in human pancreatic cancer are not well established to date. In the present study, we investigated the antiangiogenic effects of oxymatrine on human pancreatic cancer as well as the possible mechanisms involved. The results of the cell viability assay showed that treatment of PANC-1 pancreatic cancer cells with oxymatrine resulted in cell growth inhibition in a dose- and time-dependent manner. To investigate the possible mechanisms involved in these events, we performed western blotting and reverse transcription-polymerase chain reaction (RT-PCR) analysis. The results revealed that oxymatrine decreased the expression of angiogenesis-associated factors, including nuclear factor κB (NF-κB) and vascular endothelial growth factor (VEGF). Finally, the antiproliferative and antiangiogenic effects of oxymatrine on human pancreatic cancer were further confirmed in pancreatic cancer xenograft tumors in nude mice. In conclusion, our studies for the first time suggest that oxymatrine has potential antitumor effects on pancreatic cancer via suppression of angiogenesis, probably through regulation of the expression of the NF-κB-mediated VEGF signaling pathway.
Subject(s)
Alkaloids/pharmacology , Angiogenesis Inhibitors/pharmacology , Antineoplastic Agents/pharmacology , NF-kappa B/antagonists & inhibitors , Pancreatic Neoplasms/drug therapy , Quinolizines/pharmacology , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Animals , Cell Line, Tumor , Cell Survival/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , NF-kappa B/genetics , NF-kappa B/metabolism , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Signal Transduction/drug effects , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/metabolism , Xenograft Model Antitumor AssaysABSTRACT
In this study, we investigated the apoptotic effect of emodin on human pancreatic cancer cell line Panc-1 in vitro and in vivo as well as the possible mechanisms involved. In vitro, human pancreatic cancer cell line Panc-1 was exposed to varying concentrations of emodin (0, 10, 20, 40 or 80 µmol/l). Then the mitochondrial membrane potential (MMP) was analyzed by JC-1 staining, cell apoptosis was analyzed by flow cytometry (FCM) and cell proliferation was analyzed by MTT. In vivo, nude mice orthotopically implanted were randomly divided into five groups to receive treatments by different doses of emodin: control group (normal saline 0.2 ml), E10 group (emodin 10 mg/kg), E20 group (emodin 20 mg/kg), E40 group (emodin 40 mg/kg) and E80 group (emodin 80 mg/kg). Each mouse was treated 5 times by intraperitoneal injection of emodin every 3 days. During the treatment, the feeding stuff was recorded. One week after the last treatment, we recorded the body weight and the maximum diameter of tumor in each group before the mice were sacrificed. Then the cell apoptosis of the tumor was tested by TUNEL assay. The results in vitro showed that the MMP of the cells declined and the apoptosis rate increased with the emodin concentration increasing and the cell proliferation of each group was inhibited in a dose- and time-dependent manner by emodin. The feeding stuff curve did not decline significantly in E40 group and the apoptosis rate of the tumor cells in this group was higher than the lower-dose groups. Taken together, our results demonstrate that emodin may induce the pancreatic cancer cell apoptosis via declining the MMP and a moderate dose of emodin improved the living state of the model mice.
Subject(s)
Apoptosis/drug effects , Emodin/pharmacology , Membrane Potential, Mitochondrial/drug effects , Pancreatic Neoplasms/drug therapy , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Eating , Emodin/administration & dosage , Emodin/therapeutic use , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/physiopathology , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic useABSTRACT
The perioperative environment is a complex, high risk environment that requires real-time coordination by all perioperative team members and accurate, up-to-date information for situation assessment and decision-making. There is the need for a "Gestalt" holistic awareness of the perioperative environment to enable synthesis and contextualization of the salient information such as: patient information, case and procedure information, staff information, operative site view, physiological data, resource availability. One potential approach is to augment the medical toolkit with a large screen wall display that integrates and makes accessible information that currently resides in different data systems and care providers. The objectives are to promote safe workflows, team coordination and communication, and to enable diagnosis, anticipation of events, and information flow from upstream to downstream care providers. We used the human factors engineering design process to design and develop a display that provides a common operational picture for shared virtual perioperative team situation awareness to enhance patient safety.