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Cited by 158Photodynamic Therapy Research StudiesPorphyrin Metabolism and DisordersPorphyrin and Phthalocyanine Chemistry

Aminolevulinic Acid-Based Tumor Detection and Therapy: Molecular Mechanisms and Strategies for Enhancement

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Yang, Xue, Palasuberniam, Pratheeba, Kraus, Daniel, Chen, Bin·2015·International Journal of Molecular Sciences
DOI 10.3390/ijms161025865PMC PMC4632830
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Abstract

Aminolevulinic acid (ALA) is the first metabolite in the heme biosynthesis pathway in humans. In addition to the end product heme, this pathway also produces other porphyrin metabolites. Protoporphyrin (PpIX) is one heme precursor porphyrin with good fluorescence and photosensitizing activity. Because tumors and other proliferating cells tend to exhibit a higher level of PpIX than normal cells after ALA incubation, ALA has been used as a prodrug to enable PpIX fluorescence detection and photodynamic therapy (PDT) of lesion tissues. Extensive studies have been carried out in the past twenty years to explore why some tumors exhibit elevated ALA-mediated PpIX and how to enhance PpIX levels to achieve better tumor detection and treatment. Here we would like to summarize previous research in order to stimulate future studies on these important topics. In this review, we focus on summarizing tumor-associated alterations in heme biosynthesis enzymes, mitochondrial functions and porphyrin transporters that contribute to ALA-PpIX increase in tumors. Mechanism-based therapeutic strategies for enhancing ALA-based modalities including iron chelators, differentiation agents and PpIX transporter inhibitors are also discussed.

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  • High PpIX tumor accumulation is certainly related to or may even be the consequence of altered glucose and iron metabolism in tumors.

    “As heme biosynthesis is deeply intertwined with glucose and iron metabolism, high PpIX tumor accumulation is certainly related to or may even be the consequence of altered glucose and iron metabolism in tumors [167].”

    From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [167]

    Section 3.2 links altered glucose metabolism to increased tumor ALA-PpIX, but describes the proposed mechanism as a hypothesis needing further study, rather than a certain relationship. Sections 2 and 4.1 explain that iron is needed to convert PpIX to heme and that iron chelation can increase PpIX; they do not establish that altered iron metabolism in tumors causes their high PpIX accumulation. (LLM, conf=0.87)

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Authors
Yang, X., Palasuberniam, P., Kraus, D., & Chen, B.
Affiliations
University of the Sciences (US)
Corresponding author
Chen, Bin
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2015-10-28
Volume
16
Issue
10
Pages
25865-25880
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms161025865
PMC
PMC4632830
OpenAlex
W1891095862
Cited by
158
References
92
Citations by year
2026: 8 · 2025: 11 · 2024: 10 · 2023: 19 · 2022: 17 · 2021: 10 · 2020: 27 · 2019: 16 · 2018: 18 · 2017: 15 · 2016: 5 · 2015: 1
FWCI
2.31
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
American Cancer Society (RSG-10-035-01-CCE)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
  • Physical Sciences › Materials Science › Materials Chemistry › Porphyrin and Phthalocyanine Chemistry
Keywords
5-aminolevulinic acid, protoporphyrin IX, heme biosynthesis, photodynamic therapy, mitochondrial function, iron chelators, cancer metabolism
MeSH terms
Aminolevulinic Acid, Animals, Heme, Humans, Neoplasms, Photochemotherapy, Protoporphyrins, Photosensitizing Agents

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