title: eEF1A1 binds and enriches protoporphyrin IX in cancer cells in 5-aminolevulinic acid based photodynamic therapy.
abstract: Photodynamic therapy (PDT) with protoporphyrin IX (PpIX), which is endogenously derived from 5-aminolevulinic acid (5-ALA) or its derivatives, is a promising modality for the treatment of both pre-malignant and malignant lesions. However, the mechanisms of how ALA-induced PpIX selectively accumulated in the tumors are not fully elucidated. Here we discovered that eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) interacted with PpIX (with an affinity constant of 2.96 × 10(6) M(-1)). Microscopy imaging showed that ALA-induced PpIX was co-localized with eEF1A1 in cancer cells. eEF1A1 was found to enrich ALA-induced PpIX in cells by competitively blocking the downstream bioavailability of PpIX. Taken together, our study discovered eEF1A1 as a novel photosensitizer binding protein, which may play an essential role in the enrichment of ALA-induced PpIX in cancer cells during PDT. These suggested eEF1A1 as a molecular marker to predict the selectivity and efficiency of 5-ALA based PDT in cancer therapy.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|Division of Inflammation Biology, La Jolla Institute for Allergy &Immunology, La Jolla, California, USA.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|Laboratory of Molecular Immunology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wei
authors.affiliation: Cell Death and Survival Networks Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China.
authors.forename: Buhong
authors.initials: B
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Urology, Changhai Hospital, Second Military University, Shanghai, China.
authors.forename: Huamao
authors.initials: H
authors.lastname: Ye
authors.affiliation: Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|Laboratory of Molecular Immunology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Naishuo
authors.initials: N
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Xunbin
authors.initials: X
authors.lastname: Wei
mesh_terms: D000622:Aminolevulinic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D002460:Cell Line; D015723:Gene Library; D056945:Hep G2 Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020648:Peptide Elongation Factor 1 / Q000235:genetics* / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D011485:Protein Binding; D011524:Protoporphyrins / Q000378:metabolism*
chemical_list: C094814:EEF1A1 protein, human; D020648:Peptide Elongation Factor 1; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX