title: A new naturally derived photosensitizer and its phototoxicity on head and neck cancer cells.
abstract: In our screening for photosensitizers from natural resources, 15(1)-hydroxypurpurin-7-lactone ethyl methyl diester (compound 1) was isolated for the first time from an Araceae plant. To evaluate the efficacy of compound 1 as a photosensitizer for head and neck cancers, compound 1 was studied in reference to a known photosensitizer pheophorbide-a (Pha), in terms of photophysical properties, singlet oxygen generation and in in vitro experiments (intracellular uptake and phototoxicity assays) in two oral (HSC2 and HSC3) and two nasopharyngeal (HK1 and C666-1) cancer cell lines. In this study, compound 1 exhibited higher intracellular uptake over 24 h compared with Pha in both HSC3 and HK1 cells. When activated by ≥4.8 J cm(-2) of light, compound 1 was slightly more potent as a photosensitizer than Pha by consistently having marginally lower IC(50) values across different cell lines. In flow cytometry experiments to study the mechanism of photoactivated cell death in HSC3, compound 1 was observed to induce more pronounced apoptosis compared with Pha, which may have been driven by the transient G(2)/M cell cycle block which was also observed. These promising results on compound 1 warrant its further investigation as a clinically useful photodynamic therapy agent for head and neck cancer.
authors.affiliation: Cancer Research Initiatives Foundation (CARIF), Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia.
authors.forename: Siang Hui
authors.initials: SH
authors.lastname: Lim
authors.forename: Hong Boon
authors.initials: HB
authors.lastname: Lee
authors.forename: Anthony Siong Hock
authors.initials: AS
authors.lastname: Ho
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D029064:Araceae / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002734:Chlorophyll / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000737:chemistry / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008027:Light; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000378:metabolism; D013057:Spectrum Analysis
chemical_list: D004952:Esters; D007783:Lactones; D017319:Photosensitizing Agents; D010936:Plant Extracts; D002734:Chlorophyll; D026082:Singlet Oxygen; C032623:pheophorbide a