Genoprotective role of pembrolizumab liposome in isolated lymphocytes from head and neck squamous cell carcinoma patients compared to those from healthy individuals in vitro .
Nagah BobtinaMaysa AlhawamdehKhaled HabasMohamed IsrebBayan AburasAndrew T HarrisMojgan NajafzadehDiana AndersonPublished in: Nanotoxicology (2024)
Pembrolizumab has shown significant anticancer effects against various human cancers. The present study investigated the effects of pembrolizumab liposome and nano (naked) forms in treated lymphocytes from head and neck squamous cell carcinoma (HNSCC) patients compared to healthy individuals. The level of oxidative DNA damage induced by hydrogen peroxide (H 2 O 2 ) was also investigated. A concentration of 10 µg/ml of pembrolizumab liposome was used to treat the lymphocytes in the Comet and micronucleus assays based on the preliminary dosage optimization tests. To determine the cellular pathways involved in the protective role of pembrolizumab against H 2 O 2 , several proteins involved in apoptosis (P53, P21 and Bcl-2) were assessed. Pembrolizumab significantly reduced DNA damage and decreased the number of micronuclei in lymphocytes from HNSCC patients (p < 0.01) compared with healthy individuals. The 10 µg/ml of pembrolizumab liposome significantly reduced the oxidative stress induced by H 2 O 2 and was effective in healthy and HNSCC groups using the Comet and micronucleus assays (p < 0.001). To our knowledge, this is the first report of pembrolizumab in liposome and naked forms exhibiting a protective effect on DNA damage in the treatment of HNSCC patients.
Keyphrases
- dna damage
- oxidative stress
- end stage renal disease
- advanced non small cell lung cancer
- ejection fraction
- hydrogen peroxide
- newly diagnosed
- chronic kidney disease
- healthcare
- prognostic factors
- nitric oxide
- high throughput
- ischemia reperfusion injury
- cell death
- mass spectrometry
- induced apoptosis
- cell cycle arrest
- heat shock protein
- combination therapy