title: Low-dose arsenic trioxide enhances 5-aminolevulinic acid-induced PpIX accumulation and efficacy of photodynamic therapy in human glioma.
abstract: Among glioma treatment strategies, 5-aminolevulinic acid (5-ALA)-based fluorescence-guided resection (FGR) and photodynamic therapy (PDT) have been used as effective novel approaches against malignant glioma. However, insufficient intracellular protoporphyrin IX (PpIX) accumulation limits the application of FGR and PDT in the marginal areas of gliomas. To overcome these issues, we assessed the intracellular levels of PpIX in human glioma cell lines and rat cortical astrocytes pretreated with 0.1μM arsenic trioxide (ATO). Apoptosis and cell viability after PDT were evaluated using Annexin V-FITC apoptosis detection kit and MTT assay, respectively. In order to find out the possible mechanism, we investigated the expression of the key enzymes in the heme biosynthesis pathway, which regulates porphyrin synthesis in glioma cells. Our findings showed that the 5-ALA-induced PpIX accumulation in glioma cell lines pretreated with 0.1μM ATO was increased relative to the control groups. No changes in fluorescence intensity were detected in the rat cortical astrocytes pretreated using the same ATO concentration. Apoptosis following PDT in glioma cells pretreated with 0.1μM ATO were significantly higher than in control groups, especially late apoptotic cells, while the cell viability was decreased. The expression of CPOX was upregulated in glioma cells after pretreatment with 0.1μM ATO. We concluded that ATO was a potential optional approach in enhancing intracellular PpIX accumulation and improving the benefits of 5-ALA-induced FGR and PDT in glioma.
authors: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China; Institute of Brain Science, Harbin Medical University, Heilongjiang Province, People's Republic of China; The Chinese-German Center of Academic Excellence in Neuroscience, Harbin, Heilongjiang Province, People's Republic of China.
authors: Chunlei
authors: C
authors: Wang
authors: Xiaofeng
authors: X
authors: Chen
authors: Jianing
authors: J
authors: Wu
authors: Huailei
authors: H
authors: Liu
authors: Zhiyong
authors: Z
authors: Ji
authors: Huaizhang
authors: H
authors: Shi
authors: Cheng
authors: C
authors: Gao
authors: Dayong
authors: D
authors: Han
authors: Ligang
authors: L
authors: Wang
authors: Yaohua
authors: Y
authors: Liu
authors: Guang
authors: G
authors: Yang
authors: Changyu
authors: C
authors: Fu
authors: Huadong
authors: H
authors: Li
authors: Dongzhi
authors: D
authors: Zhang
authors: Ziyi
authors: Z
authors: Liu
authors: Xianfeng
authors: X
authors: Li
authors: Fei
authors: F
authors: Yin
authors: Shiguang
authors: S
authors: Zhao
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006418:Heme / Q000096:biosynthesis; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D010087:Oxides / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000378:metabolism* / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000378:metabolism* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001152:Arsenicals; D010087:Oxides; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D006418:Heme; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D000077237:Arsenic Trioxide
keywords: 5-Aminolevulinic acid; Arsenic trioxide; Glioma; Photodynamic therapy; Protoporphyrin IX