Aminolevulinic acid–based photodynamic therapy (ALA-PDT) has emerged as a new alternative for chemotherapy in cancer treatment due to its high specificity and low side effects. We added siRNAs and inhibitors of transporters to study the roles of transporters in ALA uptake in sets of normal and cancer cell lines. PEPT1 and PAT1 were expressed only in normal lung and prostate cells, respectively, but not in their cancerous counterparts. Inhibition of these transporters showed a significant decrease in PpIX production only in normal cells. PEPT1 and PAT1 transporter inhibitors could be possible new drugs to increase the specificity of ALA-PDT.
Mitochondria play a fundamental role in generating of energy in cells. Electron transfer in electron transport chain (ETC) involved in mitochondria was one of the biological functions of heme. Heme biosynthesizes increased upon the addition of 5-aminolevulinic acid (ALA). Complex I and II protein expression were downregulated, while complex IV and cytochrome c expression were upregulated by the addition of ALA. Administration of ALA significantly increased Complex IV (COX) activity and cellular ATP level. Surprisingly, the mitochondrial content and mitochondrial membrane potential were unchanged. Consistently, the relative mRNA-expression of transcription factors affecting mitochondrial biogenesis was unchanged after the addition of ALA.
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