Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy

Nakayama, Taku; Otsuka, Saori; Kobayashi, Tatsuya; Okajima, Hodaka; Matsumoto, Kentaro; Hagiya, Yuichiro; Inoue, Keiji; Shuin, Taro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun

doi:10.1038/srep36478

Cited by 49 publications

(53 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There are also FDA-approved precursors of photosensitizers, e.g. δ-aminolevulinic acid (ALA; Levulan) and methyl aminolevulinate (Metvix): After a few hours of topical application of these precursordrugs, they are integrated in the inherent biosynthetic pathway of cellular synthesis of protoporphyrin IX (PPIX), a photosensitizer [191]. In this way, dormant and hyperactive cancer cells and malignant lesions may be localized, as these cells have an upregulated biosynthesis of PPIX.…”

Section: Principles Of Photodynamic Therapy With Peptide-photosensitimentioning

confidence: 99%

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

Eberlé

Rout

et al. 2017

CMC

View full text Add to dashboard Cite

Peptides play decisive roles in the skin, ranging from host defense responses to various forms of neuroendocrine regulation of cell and organelle function. Synthetic peptides conjugated to radionuclides or photosensitizers may serve to identify and treat skin tumors and their metastatic forms in other organs of the body. In the introductory part of this review, the role and interplay of the different peptides in the skin are briefly summarized, including their potential application for the management of frequently occurring skin cancers. Special emphasis is given to different targeting options for the treatment of melanoma and melanotic lesions. Radionuclide Targeting: α-Melanocyte-stimulating hormone (α-MSH) is the most prominent peptide for targeting of melanoma tumors via the G protein-coupled melanocortin-1 receptor that is (over-)expressed by melanoma cells and melanocytes. More than 100 different linear and cyclic analogs of α-MSH containing chelators for 111In, 67/68Ga, 64Cu, 90Y, 212Pb, 99mTc, 188Re were synthesized and examined with experimental animals and in a few clinical studies. Linear Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2 (NAP-amide) and Re-cyclized Cys- Cys-Glu-His-D-Phe-Arg-Trp-Cys-Arg-Pro-Val-NH2 (Re[Arg11]CCMSH) containing different chelators at the N- or C-terminus served as lead compounds for peptide drugs with further optimized characteristics. Alternatively, melanoma may be targeted with radiopeptides that bind to melanin granules occurring extracellularly in these tumors. Photosensitizer targeting: A more recent approach is the application of photosensitizers attached to the MSH molecule for targeted photodynamic therapy using LED or coherent laser light that specifically activates the photosensitizer. Experimental studies have demonstrated the feasibility of this approach as a more gentle and convenient alternative compared to radionuclides.

show abstract

Section: Principles Of Photodynamic Therapy With Peptide-photosensitimentioning

confidence: 99%

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

Eberlé

Rout

et al. 2017

CMC

View full text Add to dashboard Cite

show abstract

“…Several studies have shown that dormant cancer cells accumulate high PpIX levels and are sensitive to ALA-PDT. Furthermore, efficacy can be strengthened by combining with G0/G1 phase arrestors [74]. These studies collectively indicate that development of new drugs that directly target and kill dormant cells may be an alternative to awakening dormant cells, which potentially represents a more translational strategy.…”

Section: Other Methodsmentioning

confidence: 93%

Research progress on therapeutic targeting of quiescent cancer cells

Zhang

Gan

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

Cellular quiescence (G0) is a sleep-like cellular state that allows cells to maintain the ability to re-enter and exit the proliferative cycle. Quiescent cancer cells are considered a therapeutic challenge since they are often resistant to conventional chemoradiotherapy resulting in disease progression and relapse. To date, the majority of published studies have focused on identifying molecules that target proliferating tumor cells while limited information is available on methods to target quiescent cancer cells. This review provides a summary of the relevant molecular mechanisms underlying quiescence maintenance and pharmacological interventions aimed at either eliminating this cancer cell subpopulation or indefinitely maintaining the quiescence state. Furthermore, the irradiation responses of quiescent cancer cells, in particular, the influence of manipulating intratumor hypoxia and radiation properties on radiosensitivity, are discussed. The main aim of this article is to provide a theoretical basis for the effective targeted killing of dormant tumor cells. ARTICLE HISTORY

show abstract

“…Although FDA-approved, the narrow window of active concentrations in our study, increased duration of time required to convert to PPIX, and localization only in the mitochondria suggest potential for improvements. Additionally, the efficacy of 5-ALA in various tumors is also dependent on the activity of the efflux pump ABCG2 [40], thereby being inversely proportional. In our study, Pd(T4) exhibited oncolytic activity as soon as 5 min pre-illumination, which is significantly shorter than previously recorded at 2 h [41].…”

Section: Discussionmentioning

confidence: 99%

Metalloporphyrin Pd(T4) Exhibits Oncolytic Activity and Cumulative Effects with 5-ALA Photodynamic Treatment against C918 Cells

Leviskas

Vályi-Nagy

Munirathinam

et al. 2020

IJMS

View full text Add to dashboard Cite

Photodynamic therapy is a non-invasive method where light activates a photosensitizer bound to cancer cells, generating reactive oxygen species and resulting in cell death. This study assessed the oncolytic potential of photodynamic therapy, comparing European Medicines Agency and United States Food and Drug Administration-approved 5-aminolevulinic acid (5-ALA) to a metalloporphyrin, Pd(T4), against a highly invasive uveal melanoma cell line (C918) in two- and three-dimensional models in vitro. Epithelial monolayer studies displayed strong oncolytic effects (>70%) when utilizing Pd(T4) at a fraction of the concentration, and reduced pre-illumination time compared to 5-ALA post-405 nm irradiance. When analyzed at sub-optimal concentrations, application of Pd(T4) and 5-ALA with 405 nm displayed cumulative effects. Lethality from Pd(T4)-photodynamic therapy was maintained within a three-dimensional model, including the more resilient vasculogenic mimicry-forming cells, though at lower rates. At high concentrations, modality of cell death exhibited necrosis partially dependent on reactive oxygen species. However, sub-optimal concentrations of photosensitizer exhibited an apoptotic protein expression profile characterized by increased Bax/Bcl-2 ratio and endoplasmic stress-related proteins, along with downregulation of apoptotic inhibitors CIAP-1 and -2. Together, our results indicate Pd(T4) as a strong photosensitizer alone and in combination with 5-ALA against C918 cells.

show abstract

Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy

Cited by 49 publications

References 45 publications

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions

Research progress on therapeutic targeting of quiescent cancer cells

Metalloporphyrin Pd(T4) Exhibits Oncolytic Activity and Cumulative Effects with 5-ALA Photodynamic Treatment against C918 Cells

Contact Info

Product

Resources

About