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Cited by 35Photodynamic Therapy Research StudiesNanoplatforms for cancer theranosticsOvarian cancer diagnosis and treatment

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Efficacy of a methyl ester of 5-aminolevulinic acid in photodynamic therapy for ovarian cancers

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Wakui, M., Yokoyama, Yoshihito, Wang, H., Shigeto, T., Futagami, M., Mizunuma, H.·2010·Journal of Cancer Research and Clinical Oncology
DOI 10.1007/s00432-010-0761-7PMC PMC11828223
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Abstract

Purpose Photodynamic therapy (PDT) is a new approach to cancer treatment that utilizes photochemical reactions induced by a combination of an oncophilic photosensitizing agent and laser light. With an aim to apply PDT for intraperitoneal disseminated foci of advanced or recurrent ovarian cancers, the present study was conducted to evaluate the antitumor effect of PDT using a methyl ester of 5-aminolevulinic acid (Methyl-ALA) on various types of human ovarian cancer in a subcutaneous xenograft model in nude mice and to elucidate the mechanism of its antitumor effect. Methods HTOA, MCAS, and TOV21G cell lines derived from human ovarian serous, mucinous, and clear cell adenocarcinoma, respectively, were used in this study. The mice in the treatment group and in the control group received an intraperitoneal injection of 250 mg/kg of Methyl-ALA and PBS alone, respectively. PDT was administered by 10 min irradiation using a 150 W halogen light, 3 h after Methyl-ALA or PBS injection. Each mouse received PDT twice a week for 3 weeks. Results Methyl-ALA-PDT significantly suppressed the growth of HTOA tumors as compared to control, whereas there was no significant effect on the growth of MCAS or TOV21G tumors. Methyl-ALA-PDT significantly increased apoptosis in implanted HTOA tumors as well as cultured cells. Western blot analysis showed that amount of expression of milk fat globule-EGF-factor 8, which binds to apoptotic cells and thereby facilitates their phagocytosis, significantly increased in HTOA tumors receiving Methyl-ALA-PDT, compared with untreated HTOA tumors. In addition, reduced vascular endothelial growth factor and CD34-positive microvessel density were found in solid HTOA tumors treated by Methyl-ALA-PDT, suggesting that the antitumor effect of Methyl-ALA-PDT is due to induction of apoptosis and reduction of angiogenesis. In comparison with HTOA cells, HPLC analysis demonstrated a significantly smaller intracellular amount of protoporphyrin IX (PpIX) in MCAS and TOV21G cells. PpIX is readily converted from Methyl-ALA and elicts photocytotoxicity. Conclusion We conclude that Methyl-ALA-PDT could be an effective treatment in ovarian cancer and should be tested to apply intraperitoneally disseminated micro-foci during surgery.

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References 22 · Cited by 35

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Metadata

Authors
Wakui, M., Yokoyama, Y., Wang, H., Shigeto, T., Futagami, M., & Mizunuma, H.
Affiliations
Hirosaki University (JP)
Corresponding author
Yokoyama, Yoshihito
ORCID
Venue
Journal of Cancer Research and Clinical Oncology
Publisher
Springer Science and Business Media LLC
Published
2010-01-13
Volume
136
Issue
8
Pages
1143-1150
ISSN
  • 0084-5353 (ISSN-L)
  • 0171-5216
  • 1432-1335
DOI
10.1007/s00432-010-0761-7
PMC
PMC11828223
OpenAlex
W2070224270
Cited by
35
References
22
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 2 · 2013: 2 · 2012: 2
FWCI
2.40
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Journal of Cancer Research and Clinical Oncology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Hirosaki University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Photodynamic Therapy Research Studies
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
  • Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
Keywords
photodynamic therapy, ovarian cancer, photosensitizers, apoptosis, angiogenesis, protoporphyrin IX, MFG-E8, tumor microvessel density, vascular endothelial growth factor, intraperitoneal dissemination, xenograft models, serous ovarian cancer, mucinous adenocarcinoma, clear cell adenocarcinoma, anticancer activity
MeSH terms
Adenocarcinoma, Aminolevulinic Acid, Animals, Cell Division, Disease Models, Animal, Female, Humans, Mice, Nude, Necrosis, Ovarian Neoplasms, Photochemotherapy, Apoptosis, Cell Line, Tumor, Mice

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