Antiproliferative effect of pheophorbide a-mediated photodynamic therapy and its synergistic effect with doxorubicin on multiple drug-resistant uterine sarcoma cell MES-SA/Dx5
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AbstractProlonged cancer chemotherapy is associated with the development of multidrug resistance (MDR), which is a major cause of treatment failure. Photodynamic therapy (PDT) has been applied as anticancer therapy and a means of circumventing MDR. The antiproliferative effect of pheophorbide a-mediated photodynamic therapy (Pa-PDT) has been demonstrated in several human cancer cell lines, including the uterine sarcoma cell line, MES-SA. This study set out to evaluate, first, the therapeutic potential of Pa-PDT on MES-SA/Dx5 uterine sarcoma cells and, subsequently, the effectiveness of combination therapy using Pa-PDT with doxorubicin (Dox). Our results showed that Pa-PDT was able to circumvent MDR in the P-glycoprotein (P-gp) overexpressing human uterine sarcoma cell line, MES-SA/Dx5. Intracellular accumulation of Pa and Pa-PDT-induced cell death was not abrogated by MDR phenotype, when compared to the parental cell line, MES-SA. Combined therapy using Pa-PDT and Dox, a common chemotherapeutic drug, was found to be synergistic in the cell line, MES-SA/Dx5. Both activity and expression of MDR1 and P-gp were reduced by Pa-PDT treatment and such reductions were attenuated by a-tocopherol, the scavenger of reactive oxygen species (ROS), suggesting that the effect of Pa-PDT was mediated by the generation of intracellular ROS. In conclusion, our findings demonstrated the therapeutic potential of Pa-PDT alone or in combination with Dox in combating multidrug-resistant malignancies.
All Author(s) ListCheung KKY, Chan JYW, Fung KP
Journal nameDrug and Chemical Toxicology
Detailed descriptiondoi:10.3109/01480545.2013.776584
Year2013
Month10
Day1
Volume Number36
Issue Number4
PublisherINFORMA HEALTHCARE
Pages474 - 483
ISSN0148-0545
LanguagesEnglish-United Kingdom
KeywordsDoxorubicin; multidrug resistance; pheophorbide a; photodynamic therapy
Web of Science Subject CategoriesChemistry; Chemistry, Multidisciplinary; CHEMISTRY, MULTIDISCIPLINARY; Pharmacology & Pharmacy; PHARMACOLOGY & PHARMACY; Toxicology; TOXICOLOGY

Last updated on 2020-31-05 at 02:38