chlorophyll-a and Uterine-Neoplasms

Prolonged 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 α-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.

Topics: alpha-Tocopherol; Analysis of Variance; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line, Tumor; Cell Proliferation; Chlorophyll; DNA Fragmentation; DNA Primers; Doxorubicin; Drug Resistance, Multiple; Drug Synergism; Female; Flow Cytometry; Humans; Photochemotherapy; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; Sarcoma; Uterine Neoplasms

Topics: Carcinosarcoma; Chlorophyll; Female; Humans; Mitochondria; Radiation-Sensitizing Agents; Uterine Neoplasms

Uterine carcinosarcoma is an aggressive neoplasm with low survival rates because of the lack of very effective chemotherapy protocol. Photodynamic therapy (PDT) is recently suggested to be an efficient protocol for this cancer. Pheophorbide a (Pa) is a chlorophyll degradation product in the green plant cells, its antitumor effect was reported on a number of human cancer cells with PDT approach. This study demonstrated that using Pa in PDT (Pa-PDT) significantly inhibited the human uterine sarcoma cell line MES-SA with an IC50 value of 0.5 μM at 24 h. Induction of apoptosis was found on the Pa-PDT treated cells according to the results of propidium iodide (PI) staining, annexin-V staining and DNA fragmentation assay. Pa was found to be localized in the mitochondria that lead to the depolarization of mitochondrial membrane potential by the rapid generation of singlet oxygen during light irradiation, where release of cytochrome c was detected and lead to the activation of intrinsic apoptotic pathway in MES-SA cells. Our findings revealed the therapeutic potential of Pa-PDT on the human uterine cancer.

Topics: Apoptosis; Biological Transport; Carcinosarcoma; Cell Line, Tumor; Cell Proliferation; Chlorophyll; Female; Humans; Mitochondria; Photochemotherapy; Radiation-Sensitizing Agents; Reactive Oxygen Species; Uterine Neoplasms

Topics: Adult; Chlorophyll; Contrast Media; Female; Humans; Iodized Oil; Lymphatic Metastasis; Lymphography; Middle Aged; Uterine Cervical Neoplasms; Uterine Neoplasms

Topics: Chlorophyll; Color; Diagnostic Techniques, Surgical; Female; Humans; Iodized Oil; Lymph Node Excision; Lymphography; Uterine Cervical Neoplasms; Uterine Neoplasms; Vulvar Neoplasms

Topics: Chlorophyll; Contrast Media; Female; Humans; Iodized Oil; Lymphatic Metastasis; Lymphography; Methods; Middle Aged; Pelvic Neoplasms; Uterine Neoplasms

Topics: Ascites; Chlorophyll; Female; Humans; Hydrothorax; Iodized Oil; Leiomyoma; Lipids; Lymphography; Meigs Syndrome; Middle Aged; Pleural Effusion; Uterine Neoplasms