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Alkylamino Phenol Derivative Induces Apoptosis by Inhibiting EGFR Signaling Pathway in Breast Cancer Cells

Tutkimustuotosvertaisarvioitu

Yksityiskohdat

AlkuperäiskieliEnglanti
Sivut809 - 819
Sivumäärä11
JulkaisuAnti-Cancer Agents in Medicinal Chemistry
Vuosikerta20
Numero7
DOI - pysyväislinkit
TilaJulkaistu - 2020
OKM-julkaisutyyppiA1 Alkuperäisartikkeli

Tiivistelmä

Background and Objective: The present study was carried out to evaluate the anticancer property ofan alkylamino phenol derivative –2-((3,4-Dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol) (THTMP) againsthuman breast cancer cells. The cytotoxicity of the THTMP was assessed to know its specificity towards breastcancer cells without affecting the normal cells.

Methods: The THTMP was synthesized and the cytotoxicity was assessed by MTT assay, Caspases enzymeactivity, DNA fragmentation and FITC/Annexin V, AO/EtBr staining, RT-PCR and QSAR. In addition, ADMEanalysis was executed to understand the mode of action of THTMP.

Results: THTMP showed potential cytotoxic activity against the growth of MCF7 and SK-BR3 cells with theIC50 values of 87.92μM and 172.51μM, respectively. Interestingly, THTMP found to activate caspase 3 andcaspase 9 enzymes in cancer cells, which are the key enzymes implicated in apoptosis. THTMP induced apoptosisin which 33% of the cells entered the late apoptotic stage after 24h of treatment. The results also revealedthat the apoptotic response could be influenced by the association of THTMP with the Epidermal Growth FactorReceptor (EGFR) mediated inhibition of the Phosphatidylinositol 3-Kinase (PI3K)/S6K1 signaling pathway. Inaddition, docking was performed to study the binding mode of the THTMP, which shows better interaction withEGFR. The structural elucidation of THTMP by Quantitative Structure-Activity Relationship model (QSAR)and ADMET screening suggested, THTMP as an effective anticancer compound.

Conclusion: This work strengthens the potential of a promising drug-like compound, THTMP, for the discoveryof anticancer drug against breast cancer.

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