Pheophorbide a based photodynamic therapy induces apoptosis via mitochondrial-mediated pathway in human uterine carcinosarcoma

Abstract

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.

The c-MET/PI3K Signaling Is Associated with Cancer Resistance to Doxorubicin and Photodynamic Therapy by Elevating BCRP/ABCG2 Expression

“…Pba was shown to cause mitochondria-dependent apoptosis in cultured cancer cells (Tang et al, 2009). In vivo animal models also demonstrated that Pba impedes tumor growth in colon carcinoma and hepatoma xenograft models (Hajri et al, 2002;Li et al, 2007).…”

“…Pba mediates mitochondrial membrane perturbation and consequent cytochrome c release, resulting in apoptotic cell death (Tang et al, 2009). In addition, PDT destroys tumor microvasculature and causes oxygen depletion within tumors (Dougherty et al, 1998).…”

Pheophorbide�a-mediated photodynamic therapy induces apoptotic cell death in murine oral squamous cell carcinoma in vitro and in vivo

“…The levels of ROS and singlet oxygen were immediately increased after Pa-PDT treatment. Singlet oxygen released from Pa-PDT mediated mitochondrial damage (15). We also determined the mitochondrial membrane potential variations (ΔΨm) with use of the fluorescence probe JC-1, the most widely implemented application for detecting mitochondrial depolarization (25).…”

“…The energy production with the use of Pa is smaller than that with other photosensitizers, which have to be excited at shorter wavelengths, therefore causing less harm to the surrounding normal tissues (19). Recent studies reported that Pa-based PDT can effectively inhibit tumor cell proliferation in several cancer cells including hepatocellular carcinoma, colon cancer, pigmented melanoma and breast adenocarcinoma (15,18,19). However, Pa-PDT treatment in OSCC has been rarely studied.…”

“…Pheophorbide a (Pa) is a chlorine based photosensitizer derived from chlorophyll-a and is one of the active components of an ethnopharmacological herb Scutellaria barbata which is commonly used for tumor treatments in Asia (15). Our group recently synthesized Pa by the removal of a magnesium ion and a phytyl group from chlorophyll-a (16).…”