Photosensitized methyl paraben induces apoptosis via caspase dependent pathway under ambient UVB exposure in human skin cells
Abstract
Methyl paraben (MP), is a widely used preservative in pharmaceutical, food and cosmetic products. Its molecular mechanism under ambient ultraviolet radiation is not well understood. We investigated photosensitizing mechanism of MP under ambient UVB (0.6 mW/cm 2 ) intensity. MP showed dose dependent decrease in cell viability of human keratinocyte cell line (HaCaT) by MTT and NRU assays. Study showed 40% reduction in antimicrobial activity of UVB irradiated MP through E. coli culture. Photosensitized MP (25 μg/ml) significantly enhanced lipid peroxidation, intracellular ROS generation and disrupted mitochondrial membrane integrity. MP induced loss of lysosomal membrane integrity and endoplasmic reticulum (ER) mediated stress evident from Ca +2 release. Phototoxicity of MP showed nuclear fragmentation, phosphatidylserine translocation, 30% tail DNA and micronuclei formation. Study showed mitochondria mediated apoptosis via upregulation of Bax, Apaf-1, Cytochrome C and Caspase-3. Upregulation of Caspase-12 (2 folds) specifically showed role of ER in apoptosis. Specific caspase inhibitor, Z-VAD-FMK showed involvement of caspase cascade pathway in apoptosis. Results indicate that photosensitive MP leads to oxidative stress mediated DNA damage and apoptosis through mitochondria and ER. MP causes deleterious effects and its long term exposure to human skin may promote skin diseases. Therefore, MP should be replaced by other photosafe preservatives for humans.
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Photosensitized methyl paraben and triclosan showed cytotoxicity, genotoxicity, arrest the cell cycle of skin cells and triggered apoptosis, and plate sensitivity test showed a reduction in antibacterial activity.
“Photosensitized methyl paraben and triclosan showed cytotoxicity, genotoxicity, arrest the cell cycle of skin cells and triggered apoptosis as well as plate sensitivity test showed a reduction in antibacterial activity”
From Skin protection from solar ultraviolet radiation using natural compounds: a review (2024) · cites this paper as Dubey et al. 2017
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Dai, D.-F., Johnson, S. C., Villarin, J. J., Chin, M. T., Nieves-Cintrón, M., Chen, T., Marcinek, D. J., Dorn, G. W., Kang, Y. J., Prolla, T. A., et al. (2011) · Circulation Research · doi:10.1161/circresaha.110.232306 · Cited by 527 · see citing works
Wäster, P. K., & Öllinger, K. M. (2009) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.421 · Cited by 72 · see citing works
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Review of the safety of application of cosmetic products containing parabens
Matwiejczuk, N., Galicka, A., & Brzóska, M. M. (2020) · Journal of Applied Toxicology · doi:10.1002/jat.3917 · Cited by 166 · see citing works
Skin protection from solar ultraviolet radiation using natural compounds: a review
Verma, A., Zanoletti, A., Kareem, K. Y., Adelodun, B., Kumar, P., Ajibade, F. O., Silva, L. F. O., Phillips, A. J., Kartheeswaran, T., Bontempi, E., et al. (2024) · Environmental Chemistry Letters · doi:10.1007/s10311-023-01649-4 · Cited by 102 · see citing works
Self-citation
- Authors
- Dubey, D., Chopra, D., Singh, J., Srivastav, A. K., Kumari, S., Verma, A., & Ray, R. S.
- Affiliations
- Babu Banarasi Das University (IN)
- Indian Institute of Toxicology Research (IN)
- Corresponding author
- Ray, Ratan Singh
- Venue
- Food and Chemical Toxicology
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 108
- Issue
- Pt A
- Pages
- 171-185
- ISSN
- 0278-6915 (ISSN-L)
- OpenAlex
- W2741329135
- Cited by
- 53
- References
- 2
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 6 · 2023: 10 · 2022: 3 · 2021: 2 · 2020: 10 · 2019: 9 · 2018: 4 · 2017: 2
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-10-01)
- Open access
- closed
- Locations
- Food and Chemical Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- CSIR-Network project INDEPTH (BSC0111)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Keywords
- methylparaben, photosensitization, UV-B radiation, phototoxicity, apoptosis, caspase-3, caspase-12, endoplasmic reticulum stress, mitochondrial membrane integrity, lipid peroxidation, reactive oxygen species, lysosomal membrane integrity, Bax, cytochrome c, Apaf-1, preservatives, skin toxicity, HaCaT keratinocytes, DNA damage, micronuclei
- MeSH terms
- Anti-Bacterial Agents, Cell Line, Dose-Response Relationship, Drug, Escherichia coli, Humans, Parabens, Sunlight, Ultraviolet Rays, Keratinocytes, Gene Expression Regulation, Enzymologic, Apoptosis, Oxidative Stress, Caspases
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