Novel development of 5-aminolevurinic acid (ALA) in cancer diagnoses and therapy

Ishizuka, Masahiro; Abe, Fuminori; Sano, Yuki; Takahashi, Kiwamu; Inoue, Katsushi; Nakajima, Motowo; Kohda, Takeo; Komatsu, Naoki; Ogura, Shun‐ichiro; Tanaka, Tohru

doi:10.1016/j.intimp.2010.11.029

Cited by 228 publications

(237 citation statements)

References 90 publications

Supporting

Mentioning

218

Contrasting

Order By: Relevance

“…Therefore, the cytotoxic effects of ALA would only be evident in tumor cells. Moreover, no side-effect of ALA has been reported in normal cells (9). These findings support ALA as a high-potential, tumor-specific antitumor agent.…”

Section: Discussionsupporting

confidence: 71%

“…ALA is widely used in tumor therapy (photodynamic therapy) and diagnosis (photodynamic diagnosis) since tumor cell-specific fluorescent porphyrin accumulates following ALA administration (9). However, ALA has not yet been considered as a therapeutic drug.…”

Section: Discussionmentioning

confidence: 99%

“…In animal cells, ALA is generated from glycine and succinyl CoA by the ALA synthase in the mitochondria. ALA administration induces the cancer-specific accumulation of fluorescent porphyrins (9). Therefore, fluorescence diagnosis, also named photodynamic diagnosis, is based on the different ALA-induced fluorescent signatures of normal and cancer tissues (10).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis

et al. 2013

Self Cite

View full text Add to dashboard Cite

Abstract. Our previous study demonstrated that 5-aminolevulinic acid (ALA) administered to mice stimulates oxidative phosphorylation by upregulation of the mitochondrial respiratory chain complex IV enzyme cytochrome c oxidase (COX). The present study investigated whether ALA disrupts the Warburg effect, which represents a shift in ATP generation from oxidative phosphorylation to glycolysis, protecting tumor cells against oxidative stress-mediated apoptosis. The human lung carcinoma cell line A549 exposed to ALA exhibited enhanced oxidative phosphorylation, which was indicated by an increase in COX protein expression and oxygen consumption. Furthermore, ALA suppressed glycolysis-mediated acidosis. This normalization of the ATP metabolic pathways significantly increased the generation of superoxide anion radical (O 2 •-) and the functional expression of active caspase-3, leading to caspase-dependent apoptosis. These data demonstrate that ALA inhibits the Warburg effect and induces cancer cell death. Use of this endogenous compound might constitute a novel approach to cancer therapy.

show abstract

Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…5-ALA itself does not serve as PS but a natural biological precursor in the heme biosynthetic pathway, which produces protoporphyrin IX (Pp IX), an intrinsic and safe PS (Peng et al, 1997;Davila, 2011;Ishizuka et al, 2011). 5-ALA induces effective accumulation of PS Pp IX in tumor cell and has high clearance rate in vivo without phototoxicities.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Anticancer Activity of 5-Aminolevulinic Acid Photodynamic Therapy in Combination with Low-dose Cisplatin on Hela Cells

Wei¹,

Ma²,

Liu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

“…It would result in good functioning of organs or tissues. However, no such ideal method has been devised yet, although there are scattered reports of the use of various kinds of fluorescence dyes towards achieving this purpose [1][2][3][4][5]. The present review paper introduces one such ideal agent that could aid surgeons in realizing their dream: acridine orange (AO).…”

Section: Introductionmentioning

confidence: 99%

Intraoperative Photodynamic Surgery (iPDS) with Acridine Orange for Musculoskeletal Sarcomas

Kusuzaki¹,

Matsubara²,

Satonaka³

et al. 2014

Cureus

View full text Add to dashboard Cite

We recently established the new limb salvage modality of acridine orange (AO) therapy (AOT), in an attempt to develop minimally invasive limb salvage surgery with minimal damage of normal tissues and a low risk of local recurrence. The treatment modality consists of intraoperative photodynamic surgery (iPDS) and photodynamic therapy (iPDT), followed by postoperative radiodynamic therapy (RDT) using AO for patients with high-grade malignant musculoskeletal sarcomas. Clinical results have shown that the treatment is associated with a low risk of local recurrence, the risk being almost the same as that following conventional wide resection, and yields superior limb function as compared to that obtained after wide resection.In this review, we present the detailed mechanism of selective accumulation of AO in sarcomas, which is related to the acidic environment and lysosomal acidity of the tumor cells induced by cancer-specific glycolysis not involving the define tricarboxylic acid (TCA) cycle (Warburg's effect). We also describe the clinical uses of AOT and the procedure for intraoperative photodynamic surgery (iPDS) using local administration of AO.

show abstract

Novel development of 5-aminolevurinic acid (ALA) in cancer diagnoses and therapy

Cited by 228 publications

References 90 publications

The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis

The heme precursor 5-aminolevulinic acid disrupts the Warburg effect in tumor cells and induces caspase-dependent apoptosis

Synergistic Anticancer Activity of 5-Aminolevulinic Acid Photodynamic Therapy in Combination with Low-dose Cisplatin on Hela Cells

Intraoperative Photodynamic Surgery (iPDS) with Acridine Orange for Musculoskeletal Sarcomas

Contact Info

Product

Resources

About