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Inhibition of human hepatocellular carcinoma HepG2 by phthalocyanine photosensitiser ZnPcS(2)P(2): ROS production, apoptosis, cell cycle arrest.
MedLine Citation:
PMID:  22265427     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Photodynamic therapy (PDT) has been accepted as an alternative treatment for cancer. The rationale for the development of PDT for cancer is that target specificity can be achieved by controlling the location at which light activates the drug, i.e. photosensitiser. Metal phthalocyanines represent a new class of photosensitisers developed for cancer treatment. In the present study, we focused on exploring molecular mechanisms of the lead photosensitiser ZnPcS(2)P(2) on hepatocellular carcinoma (HCC) HepG2 cells to guide our future development of ZnPcS(2)P(2). Growth inhibition potency of ZnPcS(2)P(2) and its analogues was tested in vitro with and without irradiation at wavelength 670nm. Irradiation shifted the concentration-growth inhibition curves of ZnPcS(2)P(2) to the left and decreased the IC(50)s of ZnPcS(2)P(2) required to produce equivalent inhibition by 200-fold on various cell lines. The amphipathic ZnPcS(2)P(2) permeated through HepG2 cell membrane and predominately distributed to lysosome and mitochondria, where it significantly reduced mitochondrial membrane potential (ΔΨm) and increased caspase-3 activity in a concentration-dependent manner after irradiation. Early apoptosis of HepG2 occurred followed by necrosis when concentrations of ZnPcS(2)P(2) were increased in the presence of irradiation. Reactive oxygen species (ROS) production was significant following ZnPcS(2)P(2) plus irradiation treatment and cell cycle was mainly arrested at G(2)/M stage. In conclusion, ZnPcS(2)P(2), once irradiated, induces HepG2 cells into apoptosis via reducing ΔΨm, producing ROS, activating caspase-3, and causing cell arrest at G(2)/M stage. This study provides important insights into molecular mechanisms of the anti-cancer ZnPcS(2)P(2), which now is in the clinical trials II in China.
Authors:
Jingwei Shao; Jinping Xue; Yongchao Dai; Hong Liu; Lee Jia; Naisheng Chen; Jinling Huang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-19
Journal Detail:
Title:  European journal of cancer (Oxford, England : 1990)     Volume:  -     ISSN:  1879-0852     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9005373     Medline TA:  Eur J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Published by Elsevier Ltd.
Affiliation:
College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002, China.
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