title: Hypericin-mediated photodynamic therapy induces apoptosis of myoloma SP2/0 cells depended on caspase activity in vitro.
abstract: Photodynamic therapy (PDT) is becoming a promising therapeutic modality for hematological malignancies. Hypericin is a natural photosensitizer possessing anti-depressant, anti-virus and anti-cancer activities. The present study was designed to explore the effect and mechanism of hypericin-mediated PDT on the mouse multiple myeloma (MM) cells in vitro.
  
  
  
  The mouse myeloma SP2/0 cells were incubed with different concentrations of hypericin and then illuminated with different light doses. The inhibitory effect of hypericin-mediated PDT on tumor cell proliferation was assayed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method. The apoptosis related morphological changes of SP2/0 cells were observed by microscopy. The biochemical hallmarks of apoptosis such as DNA fragments, mitochondrial membrane potential changes were assessed. The expression of apoptosis related proteins were investigated by western blotting.
  
  
  
  Hypericin-mediated PDT induced the proliferation inhibition and apoptosis of tumor cells in a dose dependent manner. Tumor cells showed obvious morphological changes of apoptosis and necrosis and DNA fragmentation after treated by hypericin mediated PDT (0.025 ~ 0.05 μM). The mitochondria membrane potential in SP2/0 cells was decreased significantly after incubated with the 0.025 μM and 0.5 μM hypericin (P < 0.05). The expression level of caspase-3 was decreased, while caspase activity was elevated with the increasing drug dosage. The apoptosis of SP2/0 cells was blocked by a pan-caspase inhibitor Z-VAD-FMK and caspase-3 inhibitor Ac-DEVD-CHO.
  
  
  
  Hypericin-mediated PDT induced apoptosis mainly dependent on caspase related pathways. Hypericin-mediated PDT may be a potential and alternative therapy for MM.
authors.affiliation: Engineering Research Center of Molecular Medicine, Ministry of Education, China and School of Medicine, Huaqiao University, 269 Chenghua North Road, Quanzhou, Fujian Province 361021 China.
authors.forename: Junping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Bioscience, College of Chemistry and Life Science, Zhejiang Normal University, Jinhua, 321004 China.
authors.forename: Linxiang
authors.initials: L
authors.lastname: Shao
authors.affiliation: Department of Pathology, Second Affiliated Hospital of Fujian Medical University, Quanzhou, 36200 China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Bioscience, College of Chemistry and Life Science, Zhejiang Normal University, Jinhua, 321004 China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Lu
authors.affiliation: Engineering Research Center of Molecular Medicine, Ministry of Education, China and School of Medicine, Huaqiao University, 269 Chenghua North Road, Quanzhou, Fujian Province 361021 China.
authors.forename: Ruian
authors.initials: R
authors.lastname: Xu
keywords: Apoptosis; Caspase; Hypericin-mediated photodynamic therapy; Multiple myeloma; SP2/0 cells