Cancer 2013 July-10


Selective induction of apoptosis: promising therapy in pancreatic cancer.

Curr Pharm Des. 2013;19(12):2259-68.

Zuojia Liu1,†, Dan Li1,†, Xiliang Zheng1, Erkang Wang1,* and Jin Wang1,2,*

1State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China

2Department of Chemistry and Physics, State University of New York, Stony Brook, New York, USA



Pancreatic cancer is one of lethal and poor prognostic malignancies. Due to the absence of effective detecting methods, quite a number of efforts have been made to improve a survival advantage for treatment in patients with pancreatic cancer. Over the past decade, single-agent gemcitabine and gemcitabine-containing combinations were considered standard first-line therapies for advanced pancreatic cancer. Although these routine uses of chemotherapy failed to significantly improve survival benefit for most therapies, these trials provided insights into the molecular mechanisms involved in the development of pancreatic cancer and therefore opened up new therapeutic avenues. Apoptotic inducer as a therapeutic concept has been widely proposed and experimentally identified in some works. Some reviews have revealed that apoptosis-inducing was a promising therapy in cancers with the least side effects and more effectiveness. Apoptosis is a highly controlled physiological mechanism and proceeds through two major pathways for apoptosis-inducing. Some anticancer drugs kill cancer cells by inducing apoptosis via death receptor pathway; however, other chemotherapeutic drugs trigger apoptosis via mitochondrial pathway. In this review, we summarize briefly current chemotherapy in pancreatic cancer, describe the apoptotic mechanisms, and provide a novel therapeutic strategy by targeting Ras intermediate.

PMID: 23082976


Supplementary picture:

Zuojia Liu-png-2

Figure: Proposed model for the regulation of intrinsic mitochondrial pathway in drug-induced apoptosis. Drug increases the level of Bax protein and induces the release of cytochrome c from the mitochondria, which further activates caspase 9 and caspase 3. In addition, drug causes depletion of ΔΨm and generates ROS in cells. The altered cellular oxidative state increases cytotoxicity of drug by regulating mitochondrial permeabilization. The activation of caspase 3 and the generation of ROS finally induce the apoptosis of cells after the occurrences of externalization of phosphatidylserine, DNA fragmentation, and chromatin condensation etc.

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