Novel Erlotinib-Chalcone Hybrids Diminish Resistance in Head and Neck Cancer by Inducing Multiple Cell Death Mechanisms.
HNSCC
apoptosis
cancer
chalcone
erlotinib
hybrid
necrosis
paclitaxel
resistance
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
09 Feb 2023
09 Feb 2023
Historique:
received:
05
01
2023
revised:
03
02
2023
accepted:
07
02
2023
entrez:
25
2
2023
pubmed:
26
2
2023
medline:
3
3
2023
Statut:
epublish
Résumé
In a search for novel therapeutic options for head and neck squamous cell carcinomas (HNSCCs) generally treated with limited therapeutic success, we synthesized a series of novel erlotinib-chalcone molecular hybrids with 1,2,3-triazole and alkyne linkers and evaluated them for their anticancer activity on Fadu, Detroit 562 and SCC-25 HNSCC cell lines. Time- and dose-dependent cell viability measurements disclosed a significantly increased efficiency of the hybrids compared to the 1:1 combination of erlotinib and a reference chalcone. The clonogenic assay demonstrated that hybrids eradicate HNSCC cells in low micromolar concentrations. Experiments focusing on potential molecular targets indicate that the hybrids trigger the anticancer effect by a complementary mechanism of action that is independent of the canonical targets of their molecular fragments. Confocal microscopic imaging and real-time apoptosis/necrosis detection assay pointed to slightly different cell death mechanisms induced by the most prominent triazole- and alkyne-tethered hybrids (
Identifiants
pubmed: 36834866
pii: ijms24043456
doi: 10.3390/ijms24043456
pmc: PMC9964293
pii:
doi:
Substances chimiques
Erlotinib Hydrochloride
DA87705X9K
Chalcones
0
Chalcone
5S5A2Q39HX
Triazoles
0
Antineoplastic Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Hungarian Scientific Research Fund
ID : OTKA K_129037
Organisme : National Research, Development and Innovation Office, Hungary
ID : NVKP_16-1-2016-0036
Organisme : National Research, Development and Innovation Office, Hungary
ID : 2018-1.2.1-NKP-2018-00005
Organisme : National Research, Development and Innovation Office, Hungary
ID : NKFIH K 124813
Organisme : ELTE Thematic Excellence Programme supported by the Hungarian Ministry for Innovation and Technology
ID : SzintPlusz_1117
Organisme : Higher Education Institutions Excellence Program
ID : 2020-4.1.1.-TKP2020
Organisme : Ministry of Innovation and Technology of Hungary
ID : TKP2021-EGA-24
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