hypocrellin-b and hypericin

Photodynamic therapy (PDT) is a promising new modality in the treatment of cancers, which employs the interaction between a tumor-localizing photosensitizer and light of an appropriate wavelength to bring about molecular oxygen-induced cell death. We have investigated the efficacy of photosensitizers from the family perylenequinone, namely Hypericin, Hypocrellin A and B, in the treatment of cancer. These photosensitizers are known as potent second generation natural photosensitizers that have phototherapeutic advantages over the presently used porphyrins. We have studied the in vitro signaling mechanism involved in the photodynamic action following PDT in various human carcinoma cell lines. The difference of tumor cell death between two modes of action i.e., vascular- and cellular-mediated cell death, were evaluated in order to compare treatments that can efficaciously eradicate tumor in xenografts model. The antivascular effect of PDT was demonstrated in the chick chorioallantoic membrane (CAM) model. Tumor therapy based on targeting the vasculature of the tumor is indeed promising as demonstrated in the higher relative regression percentage of treated tumor compared to cellular targeted PDT. The favorable tumor response derived from short drug-light interval mediated PDT was primarily based on the differential uptake of the photosensitizer into tumor-associated vasculature as opposed to the cellular compartments of the tumor.

Topics: Animals; Anthracenes; Apoptosis; Blood Vessels; Humans; Neoplasms; Perylene; Phenol; Photochemotherapy; Photosensitizing Agents; Quinones

A novel carbon dot-based luminescence probe for singlet oxygen (

Topics: Animals; Anthracenes; Antineoplastic Agents; Carbon; Female; HeLa Cells; Humans; Imidazoles; Luminescence; Luminescent Agents; Methylene Blue; Mice, Inbred BALB C; Mice, Nude; Neoplasms; Perylene; Photochemotherapy; Photosensitizing Agents; Quantum Dots; Quinones; Singlet Oxygen

The chorioallantoic membrane (CAM) assay is a widely used bioassay in early in vivo cancer research. The CAM allows non-invasive study of in vivo microvasculature and blood circulation. This report describes the first topical application investigation of photodynamic response in the CAM model using Hypericin (HY) and Hypocrellin B (HB) that belongs to the perylenequinone family. Briefly, cultivated carcinoma of the human bladder cell line (MGH), were inoculated on the CAM of fertilized eggs of embryo age (EA) 9. Tumor growth was evaluated by digital stereomicroscopy. Photodynamic therapy (PDT) was performed following topical application of the photosensitizers. We were able to demonstrate that these perylenequinones localized selectively in the xenografted bladder tumor and in the vasculature of the CAM. Photodynamic treatments were performed using a custom-made non-laser light source coupled into a flexible fiber bundle to selectively excite the photosensitizers in order to induce photodamage to the tumor and vasculature. The vascular damage induced was quantitatively measured following topical application of the photosensitizers. Both photosensitizers exhibited very similar degrees of photodamage to the CAM. The CAM model offers an exciting avenue for the study of PDT induced effect on the vasculature. Our preliminary results support that the CAM model could potentially serve as a customized model to study photodynamic therapy effects of various photosensitizers on specific tumor models.

Topics: Animals; Anthracenes; Blood Vessels; Chickens; Chorioallantoic Membrane; Neoplasms; Perylene; Photochemotherapy; Photosensitizing Agents; Quinones

Potent photosensitizers hypocrellin A (HA), hypocrellin B (HB) and hypericin (HY) are lipid-soluble perylquinone derivatives of the genus Hypericum and have a strong photodynamic effect on tumors and viruses. However, the mechanisms of tumor cell death induced by HA, HB and HY are still unclear. Moreover, no reports have mentioned cell apoptosis induced by HA, HB and HY in human nasopharyngeal carcinoma (NPC) and other mucosal cells. In this study, we attempt to clarify the photodynamic effects of HA, HB and HY compounds in poorly differentiated (CNE2) and moderately differentiated (TW0-1) human NPC cells as well as human mucosal colon and bladder cells. Using these cell lines we investigated few hallmarks of apoptotic commitments in a drug dose dependent manner. Tumor cells photo-activated with HA, HB and HY showed cell size shrinkage and an increase in the sub-diploid DNA content. A loss of membrane phospholipid asymmetry associated with apoptosis was induced by all tumor cell lines as evidenced by the externalization of phosphatidylserine. Under apoptotic conditions, Western blot analysis of poly(ADP-ribose) polymerase, a caspases substrate, showed the classical cleavage pattern (116 to 85 kDa) associated with apoptosis in HA, HB and HY-treated cell lysates. In addition, 85 kDa cleaved product was blocked by the tetrapepdide caspase inhibitors such as DEVD-CHO or z-VAD-fmk. Both inhibitors protect tumor cells from apoptosis. These results demonstrate that tumor cell death induced by HA, HB and HY is mediated by caspase proteases. This study also identifies HB as a more potent and promising photosensitizer for the treatment of mucosal cancer cells.

Topics: Anthracenes; Antineoplastic Agents; Apoptosis; Caspase 3; Caspases; Cell Line; Cell Membrane; Cell Size; Cell Survival; DNA, Neoplasm; Enzyme Activation; Humans; Mucous Membrane; Nasopharyngeal Neoplasms; Perylene; Phenol; Phosphatidylserines; Photosensitizing Agents; Poly(ADP-ribose) Polymerases; Quinones; Tumor Cells, Cultured