Related Experiment Video
Updated: May 1, 2026
Determining the Toxicity of UV Radiation and Chemicals on Primary and Immortalized Human Corneal Epithelial Cells
Published on: July 22, 2021
Vandetanib-induced phototoxicity in human keratinocytes NCTC-2544
Alessia Salvador1, Daniela Vedaldi1, Paola Brun2
1Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy.
Abstract:
The phototoxicity of the new anticancer drug vandetanib was evaluated using human keratinocyte cell line, NCTC-2544. This study was started since many clinical cases of vandetanib photosensitizing reactions were recently reported in literature. Vandetanib induces a clear drop in human keratinocytes viability after cell irradiation in concentration and UV-A dose dependent mode. Since vandetanib can photolyze with the formation of two main photoproducts after UV-A exposure, the contribution of these new species was also evaluated. These two photoproducts did not have a main role in the phototoxicity of their parent drug. In our opinion, the main hypothesis for the vandetanib phototoxic potential is the formation of a very reactive specie, such as an aryl radical, which can react promptly with different targets inside the cells. In fact, a massive DNA photodamage was detected both in the in vitro DNA photocleavage experiments, and in cells. Moreover, vandetanib was able to photoinduce lipid peroxidation and protein oxidations. Vandetanib photoinduced cell death by apoptosis with the involvement of mitochondria and lysosomes.
Insights
The anticancer drug vandetanib causes significant phototoxicity in skin cells, leading to cell death. This photosensitivity is linked to DNA damage and oxidative stress, not its photoproducts.
Area of Science:
- Photobiology
- Dermatology
- Oncology
Background:
- Vandetanib is an anticancer drug with reported photosensitizing reactions.
- Clinical cases highlight the need to understand vandetanib's phototoxicity.
Purpose of the Study:
- To evaluate the phototoxicity of vandetanib in human keratinocytes.
- To investigate the mechanisms underlying vandetanib-induced photosensitivity.
Main Methods:
- Exposure of NCTC-2544 human keratinocytes to vandetanib and UV-A irradiation.
- Analysis of cell viability, photoproduct formation, DNA photodamage, lipid peroxidation, and protein oxidation.
- Assessment of apoptosis and cellular organelle involvement (mitochondria, lysosomes).
Main Results:
- Vandetanib significantly reduced keratinocyte viability in a dose- and UV-A dependent manner.
- Identified photoproducts did not significantly contribute to phototoxicity.
- Evidence suggests aryl radical formation, leading to extensive DNA photodamage, lipid peroxidation, and protein oxidation.
- Vandetanib photoinduced apoptosis via mitochondrial and lysosomal pathways.
Conclusions:
- Vandetanib exhibits significant phototoxicity mediated by reactive species formation and subsequent cellular damage.
- The primary mechanism involves DNA damage and oxidative stress, rather than photoproducts.
- Understanding these mechanisms is crucial for managing vandetanib-related photosensitivity in patients.
Related Concept Videos
01:38Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:30Drug Toxicity: Allergic Reactions