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Induction of apoptosis in HPV16 E7 transfected human keratinocyte by ALA-mediated photodynamic therapy
Abstract
Background and objective 5-Aminolevulinic acid (ALA)-mediated photodynamic therapy (ALA-PDT) is effective for the treatment of condyloma and intraepithelial neoplasia associated with human papillomaviruses (HPV). However, the mechanism of PDT on HPV-infected host cells is not fully understood. The aim of this in vitro study was to examine ALA-PDT induced apoptosis in a high-risk HPV E7 gene transfected cell line. Materials and methods HPV16 E7 gene obtained from HPV16 positive human cervical carcinoma was transfected into a human keratinocyte cell line. PpIX generation and ALA-PDT-induced apoptosis and mitochondrial damage were investigated in vitro. Results Fluorescence examination showed that HPV16E7 transfected cells could produce PpIX fairly quickly in the presence of 1mM ALA. Apoptosis occurred after ALA-PDT at dose levels of 4, 8, and 12 J/cm(2). Mitochondrial potential collapse occurred as early as 2 h post PDT. ALA-PDT induced a relatively weak and shorter caspase-9 activation but a strong and long lasting caspase-3 activation. However, mRNA levels of caspase-9 and -3 genes in cells treated with ALA-PDT were unchanged. Conclusion This in vitro study demonstrated that HPV16 E7 transfected keratinocytes could generate PpIX in the presence of ALA. Under light irradiation, ALA-PDT could induce mitochondrial-dependent apoptosis in HPV16 E7 transfected cells.
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Loss of mitochondrial membrane potential induces apoptotic cell death by activating the caspase-9-mediated mitochondrial apoptotic pathway.
“Consequently, the loss of mitochondrial membrane potential induces apoptotic cell death by activating the caspase-9-mediated mitochondrial apoptotic pathway, as shown in multiple studies with various cell lines [25,26,27,28].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [27]
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Metadata
- Authors
- Miao, F., Lv, T., Zhang, Y., Huang, Z., Wang, X., & Wang, H.
- Affiliations
- Fudan University (CN)
- Shanghai Skin Disease Hospital (CN)
- Fujian Normal University (CN)
- Corresponding author
- Wang, Hongwei
- Venue
- Photodiagnosis and Photodynamic Therapy
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 13
- Pages
- 205-210
- ISSN
- 1572-1000 (ISSN-L)
- OpenAlex
- W962310441
- Cited by
- 20
- References
- 40
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 2
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Photodiagnosis and Photodynamic Therapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Type A Major Project of Shanghai Health Bureau (20124034)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Dermatology › Nonmelanoma Skin Cancer Studies
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Keywords
- 5-aminolevulinic acid, photodynamic therapy, HPV16 E7, human papillomavirus, apoptosis, keratinocytes, protoporphyrin IX, mitochondrial depolarization, caspase-3, caspase-9, mitochondrial-dependent apoptosis
- MeSH terms
- Aminolevulinic Acid, Cell Line, Humans, Light, Photochemotherapy, Protoporphyrins, Transfection, Keratinocytes, Treatment Outcome, Apoptosis, Photosensitizing Agents, Papillomavirus E7 Proteins
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