title: RUNX3 confers sensitivity to pheophorbide a-photodynamic therapy in human oral squamous cell carcinoma cell lines.
abstract: Photodynamic therapy (PDT) with photosensitizer is one of the promising modalities for cancer treatment. For clinical use of PDT, screening process should be preceded to enhance sensitivity to PDT. Thus, we investigated a molecular biomarker to determine the sensitivity to pheophorbide a (Pa)-PDT in immortalized human oral keratinocytes (IHOK) and oral squamous cell carcinoma (OSCC) cell lines. Two IHOK and several OSCC cell lines were used. After Pa-PDT, cell viability was reduced by more than 50%, and reactive oxygen species were generated in IHOK and OSCC cell lines. Additionally, apoptosis occurred in PDT-treated cells. IHOK(S) and IHOK(P), the two IHOK cell lines derived from the same source, showed a difference in cytotoxicity after Pa-PDT. To explain this difference in cytotoxicity, we looked at the expression of Wnt signaling-related genes in these two cell lines, for the morphology of IHOK(S) which was spindle like and elongated and distinct from IHOK(P) and the parent cell. Among the relevant genes, runt-related transcription factor 3 (RUNX3), an apoptosis-related gene, was selected as a potential marker that confers sensitivity to PDT. We found that the cytotoxicity by Pa-PDT was proportional to RUNX3 expression in OSCC cell lines. Additionally, knockdown of RUNX3 expression reduced cytotoxicity by Pa-PDT, suggesting that RUNX3 might be a biomarker to determine sensitivity to Pa-PDT. This was the first study to find a new target molecule that enhances Pa-PDT effects in IHOK and OSCC cell lines. Hence, the development of a PDT-dependent biomarker could provide a novel approach to improve the effects of PDT on oral precancerous and cancerous lesions.
authors.affiliation: Department of Oral Pathology, Oral Cancer Research Institute, Brain Korea 21 Project, College of Dentistry, Yonsei University, Seoul, 120-752, South Korea.
authors.forename: Sook
authors.initials: S
authors.lastname: Moon
authors.forename: Jung Yoon
authors.initials: JY
authors.lastname: Bae
authors.forename: Hwa-Kyung
authors.initials: HK
authors.lastname: Son
authors.forename: Doo Young
authors.initials: DY
authors.lastname: Lee
authors.forename: Gyeongju
authors.initials: G
authors.lastname: Park
authors.forename: Hyun
authors.initials: H
authors.lastname: You
authors.forename: Hyojin
authors.initials: H
authors.lastname: Ko
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry; D050677:Core Binding Factor Alpha 3 Subunit / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism / Q000628:therapy*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; C493729:Runx3 protein, human; D051153:Wnt Proteins; D002734:Chlorophyll; C032623:pheophorbide a