Apoptosis induced by photosensitizers (Perylquinone derivatives) in human carcinoma cells: a possible relevance to photodynamic therapy.
Novel photosensitizers Hypocrellin A (HA) and Hypocrellin B (HB), lipid soluble perylquinone derivatives of the genus Hypericum have a strong photodynamic effect on tumors and viruses. However, the mechanisms of tumor cell death induced by HA and HB are still unclear. In this study, we attempt to elucidate the photodynamic effects of HA and HB compounds in poorly differentiated (CNE2) and moderately differentiated (TW0-1) human nasopharyngeal carcinoma (NPC) cells as well as human mucosal colon (CCL-220.1) and bladder (SD) cells. Using these cell lines we investigated few hall marks of apoptotic commitments in a drug and light dose dependent manner. Tumor cells photoactivated with HA and HB 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. Western blot analysis of poly (ADP-ribose) polymerase, a caspases substrate, showed the classical cleavage pattern (116 to 85kDa) associated with apoptosis in HA and HB-treated cell lysates. In addition, PARP cleavage was blocked by using tetrapepdide caspases inhibitors such as DEVD or z-VAD. These results demonstrate that tumor cell death induced by HB and HA is mediated by caspase proteases. This study also identifies both colon and bladder cells were more sensitive cell lines than NPC (CNE2 and TWO-1) cell lines.
Ali
Seyed Mohamed
SM
National Cancer Centre, School of Science, Singapore. dmssma@nccs.com.sg
Olivo
Malini
M
Yuen
Gan Yik
GY
Chee
Soo Khee
SK
D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000473:pathology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D003106:Colon / Q000166:cytology / Q000187:drug effects; D006801:Humans; D009092:Mucous Membrane / Q000166:cytology / Q000187:drug effects; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D019800:Phenol; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011809:Quinones / Q000494:pharmacology*; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects
D017319:Photosensitizing Agents; D011809:Quinones; D019800:Phenol; D010569:Perylene; C048388:hypocrellin A; C064522:hypocrellin B