Autophagy in pancreatic cancer: an emerging mechanism of cell death.
Summary of "Autophagy in pancreatic cancer: an emerging mechanism of cell death."
Pancreatic cancer, the fourth leading cause of cancer-related death in the United States, is resistant to current chemotherapies. Therefore, identification of different pathways of cell death is important to develop novel therapeutics. Our previous study has shown that triptolide, a diterpene triepoxide, inhibits the growth of pancreatic cancer cells in vitro and prevents tumor growth in vivo. However, the mechanism by which triptolide kills pancreatic cancer cells was not known, hence, this study aimed at elucidating it. Our study reveals that triptolide kills diverse types of pancreatic cancer cells by two different pathways; it induces caspase-dependent apoptotic death in some cell lines and death via a caspase-independent autophagic pathway in the other cell lines tested. Triptolide-induced autophagy requires autophagy-specific genes, atg5 or beclin 1 and its inhibition results in cell death via the apoptotic pathway, whereas inhibition of both autophagy and apoptosis rescues triptolide-mediated cell death. Our study shows for the first time that induction of autophagy by triptolide has a pro-death role in pancreatic cancer cells. Since triptolide kills diverse pancreatic cancer cells by different mechanisms, it makes an attractive chemotherapeutic agent for future use against a broad spectrum of pancreatic cancers.
Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
This article was published in the following journal.
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20818166
- DOI: http://dx.doi.org/10.4161/auto.6.7.13334
Overexpression of anti-apoptotic Bcl-2 proteins is commonly observed in a variety of cancers and associated with resistance to conventional chemotherapeutic drugs. Targeting multiple anti-apoptotic...
The HH signaling pathway is a 'core' signal transduction pathway in pancreatic cancer that promotes the tumorigenesis of pancreatic cancers via enhancing cell proliferation, increasing invasion and me...
Since 1940 chemotherapy has been one of the major therapies used to kill cancer cells. However, conventional standard cytotoxic agents have a low therapeutic index and often show toxicity in healthy c...
Not surprisingly, the death of a cell is a complex and well controlled process. For several decades, apoptosis, the first genetically programmed death process to be identified has taken center stage a...
AZD8055 is a potent inhibitor of mTORC1 and mTOR2 and shows inhibitory effects in several types of cancer cells in vitro and in vivo. However, the effect of AZD8055 on hepatocellular carcinoma (HCC)...
Cancer results from multiple mutations which cause cells to grow uncontrolled. It therefore may be necessary to inhibit several oncogenic targets to affect cancer cell growth. Studies ha...
The purpose of this study is to examine the combination of one standard treatment for lung cancer plus an additional drug, hydroxychloroquine. The standard treatment for lung cancer being...
This research study uses radiation or a gene therapy agent, TNFerade in addition to a dendritic cell vaccine in patients with locally advanced or low volume metastatic pancreatic cancer. T...
Chloroquine might very well be able to increase overall survival in small cell lung cancer by sensitizing cells resistant to chemotherapy and radiotherapy.
This study is designed to determine the following: 1. 1. The degree and duration of T reg suppression in patients with metastatic pancreatic cancer receiving Ontak. The goal is...
Medical and Biotech [MESH] Definitions
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A primary malignant neoplasm of the pancreatic ISLET CELLS. Usually it involves the non-INSULIN-producing cell types, the PANCREATIC ALPHA CELLS and the pancreatic delta cells (SOMATOSTATIN-SECRETING CELLS) in GLUCAGONOMA and SOMATOSTATINOMA, respectively.
Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).
Star-shaped, myofibroblast-like cells located in the periacinar, perivascular, and periductal regions of the EXOCRINE PANCREAS. They play a key role in the pathobiology of FIBROSIS; PANCREATITIS; and PANCREATIC CANCER.