Novel strategy to increase specificity of ALA-Induced PpIX accumulation through inhibition of transporters involved in ALA uptake

Lai, Hung Wei; Sasaki, Ryuta; Usuki, Shiro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun‐ichiro

doi:10.1016/j.pdpdt.2019.06.017

Cited by 14 publications

(6 citation statements)

References 34 publications

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“…After its entry into the cell, ALA is converted into PpIX and heme through a series of enzyme-mediated reactions in the cell [ 22 , 23 ]. The uptake of ALA into the cell can be determined by measuring the concentration of PpIX and heme produced using high performance liquid chromatography (HPLC) as described in the Materials & Methods.…”

Section: Resultsmentioning

confidence: 99%

Suppression of angiotensin converting enzyme 2, a host receptor for SARS-CoV-2 infection, using 5-aminolevulinic acid in vitro

et al. 2023

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Angiotensin converting enzyme 2 (ACE2), an entry receptor found on the surface of host cells, is believed to be detrimental to the infectious capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Scientists have been working on finding a cure since its outbreak with limited success. In this study, we evaluated the potential of 5-aminolevulinic acid hydrochloride (ALA) in suppressing ACE2 expression of host cells. ACE2 expression and the production of intracellular porphyrins following ALA administration were carried out. We observed the reduction of ACE2 expression and intracellular porphyrins following ALA administration. ALA suppressed the ACE2 expression in host cells which might prevent binding of SARS-CoV-2 to host cells. Co-administration of ALA and sodium ferrous citrate (SFC) resulted in a further decrease in ACE2 expression and increase in intracellular heme level. This suggests that the suppression of ACE2 expression by ALA might occur through heme production. We found that the inhibition of heme oxygenase-1 (HO-1), which is involved in heme degradation, also resulted in decrease in ACE2 expression, suggesting a potential role of HO-1 in suppressing ACE2 as well. In conclusion, we speculate that ALA, together with SFC administration, might serve as a potential therapeutic approach in reducing SARS-CoV-2 infectivity through suppression of ACE2 expression.

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Section: Resultsmentioning

confidence: 99%

Suppression of angiotensin converting enzyme 2, a host receptor for SARS-CoV-2 infection, using 5-aminolevulinic acid in vitro

et al. 2023

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“…The effect of PDT is closely related to the concentration of photosensitizers and the time of application (17). This mechanism helps PDT specifically targets and inhibits actively proliferating pathological cells, which makes it a promising alternative to cervical precancerous diseases due to its high efficacy and minimal side effects (18). Following the administration of exogenous PSs,…”

Section: Discussionmentioning

confidence: 99%

Effects of 5-aminolevulinic acid photodynamic therapy for cervical low-grade squamous intraepithelial lesions with HR-HPV infections

Li,

Chen,

et al. 2024

Front. Med.

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ObjectiveTo determine the effectiveness and safety of 5-aminolevulinic acid mediated photodynamic therapy (5-ALA PDT) in HR-HPV infected patients with cervical low-grade squamous intraepithelial lesions (LSIL) and to explore possible factors affecting treatment outcomes.MethodsThis retrospective study included 96 patients with histologically confirmed cervical LSIL and high-risk human papillomavirus (HR-HPV) infection. They received 5-ALA PDT treatment once a week for a total of 3 courses. All patients were evaluated by cytology tests, HPV DNA assay, colposcopy, and biopsy at 2 weeks, 3 months, and 6 months checkpoint. The chi-square test were used to evaluate the differences in various clinical data, and a p value <0.05 was considered statistically significant.ResultsAt 2 weeks, 3 months, and 6 months checkpoint, colposcopies showed that the cervical iodine-unstained area under VILI (visual inspection with Lugol’s iodine) significantly reduced (p < 0.01) with no structure changes. At 3 months and 6 months checkpoint, the pathological regression rate reached 87.5% (84/96) and 94.79% (91/96), while the HR-HPV clearance rates reached 80.21% (77/96) and 93.75% (90/96) respectively. We also examined the efficacy in the HPV 16/18-related group and non-HPV 16/18-related group. The HR-HPV clearance rate in the HPV16/18 group [94.87% (37/39)] was significantly higher than that of the non-HPV 16/18 group [70.17% (40/57)]. However, at 6 months after treatment, the clearance rate of the HPV 16/18 group [94.87% (37/39)] showed no statistical difference from the non-HPV 16/18 group [92.30% (53/57)].ConclusionTopical 5-ALA PDT can effectively eliminate HR-HPV infection and treat low-grade cervical squamous intraepithelial lesions, it offers an alternative treatment option for patients with LSIL, especially for those with fertility requirements and who wish to preserve cervical structure or function.

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“…Western blotting analyses were carried out as previously described ( Lai et al, 2019 ). We used polyclonal anti-human Ki-67 antibody (Abcam, Cambridge, UK; 1:1000), anti-human p21 antibody (Invitrogen, Waltham, MA, USA, 1:500), anti-human CD44 antibody (Abcam, Cambridge, UK; 1:200), anti-human GLUT1 antibody (Abcam, Cambridge, MA, USA; 1:500), anti-human GAT2 antibody (Medical & Biological Laboratories, Nagoya, Japan; 1:1000), and anti-human HSP90 antibody (Santa Cruz Biotechnology, TX, USA; 1:200 dilution) as primary antibodies.…”

Section: Methodsmentioning

confidence: 99%

Metabolic shift towards oxidative phosphorylation reduces cell-density-induced cancer-stem-cell-like characteristics in prostate cancer in vitro

et al. 2023

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Background: Numerous cancer patients undergoing conventional cancer therapies such as radiotherapy, chemotherapy and surgical tumour removal face relapses several years or even decades later. This may be due to the presence of cancer stem cells (CSCs) which survived said therapies. In this study, we aimed to uncover the relationship between cell density and CSCs, and the role of the Warburg effect in regulating CSC-like characteristics. Method: A prostate cancer cell line, PC3, was used in this study. To investigate the Warburg effect effect and CSC-like characteristics in prostate cancer, we measured the expression levels of glycolysis and OXPHOS-related genes, and performed spheroid forming, cell viability and various glycolysis and OXPHOS-assays. Results: Increase cell density caused a metabolic shift from glycolysis to OXPHOS and higher CSC-like characteristics. However, the use of dichloroacetate (DCA), an inhibitor of the Warburg effect, significantly inhibited the cell density-induced metabolic shift and CSC-like characteristics. Conclusion: Changes in cell density strongly influenced the preferred metabolic pathway of prostate cancer cells, regulating their CSC-like characteristics. It is possible that DCA, an inhibitor of the Warburg effect, could be a novel drug used to treat CSCs by distinguishing Warburg effect, preventing future cancer relapses.

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Novel strategy to increase specificity of ALA-Induced PpIX accumulation through inhibition of transporters involved in ALA uptake

Cited by 14 publications

References 34 publications

Suppression of angiotensin converting enzyme 2, a host receptor for SARS-CoV-2 infection, using 5-aminolevulinic acid in vitro

Suppression of angiotensin converting enzyme 2, a host receptor for SARS-CoV-2 infection, using 5-aminolevulinic acid in vitro

Effects of 5-aminolevulinic acid photodynamic therapy for cervical low-grade squamous intraepithelial lesions with HR-HPV infections

Metabolic shift towards oxidative phosphorylation reduces cell-density-induced cancer-stem-cell-like characteristics in prostate cancer in vitro

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