Neurotransmitter transporter family including SLC6A6 and SLC6A13 contributes to the 5-aminolevulinic acid (ALA)-induced accumulation of protoporphyrin IX and photodamage, through uptake of ALA by cancerous cells.

Abstract

δ-Aminolevulinic acid (ALA)-induced protoporphyrin accumulation is widely used in the treatment of cancer, as photodynamic therapy (PDT). To clarify the mechanisms of ALA uptake by tumor cells, we have examined the ALA-induced accumulation of protoporphyrin by the treatment of colon cancer DLD-1 and epithelial cancer HeLa cells with γ-aminobutyric acid (GABA)-related compounds. When the cells were treated with GABA, taurine and β-alanine, the level of protoporphyrin was decreased, suggesting that plasma membrane transporters involved in the transport of neurotransmitters contribute to the uptake of ALA. By transfection with neurotransmitter transporters SLC6A6, SLC6A8 and SLC6A13 cDNA, the ALA- and ALA methylester-dependent accumulation of protoporphyrin markedly increased in HEK293T cells, dependent on an increase in the uptake of ALA. When ALA-treated cells were exposed to white light, the extent of photodamage increased in SLC6A6- and SLC6A13-expressing cells. Conversely, knockdown of SLC6A6 or SLC6A13 with siRNAs in DLD-1 and HeLa cells decreased the ALA-induced accumulation. The expression of SLC6A6 and SLC6A13 was found in some cancer cell lines. Immunohistochemical studies revealed that the presence of these transporters was elevated in colon cancerous cells. These results indicated that neurotransmitter transporters including SLC6A6 and SLC6A13 mediate the uptake of ALA and can play roles in the enhancement of ALA-induced accumulation of protoporphyrin in cancerous cells.

• Authors: Tai Tien Tran, Anfeng Mu, Yuka Adachi, Yasushi Adachi, Shigeru Taketani
• Journal: Photochemistry and photobiology (Photochem Photobiol) 2014 Sep-Oct Vol. 90 Issue 5 Pg. 1136-43 ISSN: 1751-1097 [Electronic] United States
• PMID: 24842606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The American Society of Photobiology.

Chemical References

• GABA Plasma Membrane Transport Proteins
• Membrane Glycoproteins
• Membrane Transport Proteins
• Neurotransmitter Agents
• Photosensitizing Agents
• Protoporphyrins
• RNA, Small Interfering
• SLC6A13 protein, human
• beta-Alanine
• taurine transporter
• Taurine
• gamma-Aminobutyric Acid
• Aminolevulinic Acid
• protoporphyrin IX

Topics

• Aminolevulinic Acid (metabolism, pharmacology)
• Biological Transport
• Cell Line, Tumor
• Cell Survival (drug effects, radiation effects)
• GABA Plasma Membrane Transport Proteins (genetics, metabolism)
• Gene Expression
• HEK293 Cells
• HeLa Cells
• Humans
• Light
• Membrane Glycoproteins (antagonists & inhibitors, genetics, metabolism)
• Membrane Transport Proteins (genetics, metabolism)
• Neurotransmitter Agents (metabolism, pharmacology)
• Photochemotherapy
• Photosensitizing Agents (chemistry, metabolism)
• Plasmids
• Protoporphyrins (chemistry, metabolism)
• RNA, Small Interfering (genetics, metabolism)
• Taurine (metabolism, pharmacology)
• Transfection
• beta-Alanine (metabolism, pharmacology)
• gamma-Aminobutyric Acid (metabolism, pharmacology)