A small library of chalcones induce liver cancer cell death through Akt phosphorylation inhibition.
Antineoplastic Agents
/ chemistry
Apoptosis
/ drug effects
Cell Cycle
/ drug effects
Cell Death
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Chalcones
/ chemistry
Dose-Response Relationship, Drug
Drug Development
Humans
Models, Biological
Molecular Structure
Phosphorylation
/ drug effects
Proto-Oncogene Proteins c-akt
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 07 2020
16 07 2020
Historique:
received:
18
10
2017
accepted:
26
06
2020
entrez:
18
7
2020
pubmed:
18
7
2020
medline:
22
12
2020
Statut:
epublish
Résumé
Hepatocellular carcinoma (HCC) ranks as the fifth most common and the second deadliest cancer worldwide. HCC is extremely resistant to the conventional chemotherapeutics. Hence, it is vital to develop new treatment options. Chalcones were previously shown to have anticancer activities in other cancer types. In this study, 11 chalcones along with quercetin, papaverin, catechin, Sorafenib and 5FU were analyzed for their bioactivities on 6 HCC cell lines and on dental pulp stem cells (DPSC) which differentiates into hepatocytes, and is used as a model for untransformed control cells. 3 of the chalcones (1, 9 and 11) were selected for further investigation due to their high cytotoxicity against liver cancer cells and compared to the other clinically established compounds. Chalcones did not show significant bioactivity ([Formula: see text]) on dental pulp stem cells. Cell cycle analysis revealed that these 3 chalcone-molecules induced SubG1/G1 arrest. Akt protein phosphorylation was inhibited by these molecules in PTEN deficient, drug resistant, mesenchymal like Mahlavu cells leading to the activation of p21 and the inhibition of NF[Formula: see text]B-p65 transcription factor. Hence the chalcones induced apoptotic cell death pathway through NF[Formula: see text]B-p65 inhibition. On the other hand, these molecules triggered p21 dependent activation of Rb protein and thereby inhibition of cell cycle and cell growth in liver cancer cells. Involvement of PI3K/Akt pathway hyperactivation was previously described in survival of liver cancer cells as carcinogenic event. Therefore, our results indicated that these chalcones can be considered as candidates for liver cancer therapeutics particularly when PI3K/Akt pathway involved in tumor development.
Identifiants
pubmed: 32678233
doi: 10.1038/s41598-020-68775-9
pii: 10.1038/s41598-020-68775-9
pmc: PMC7367369
doi:
Substances chimiques
Antineoplastic Agents
0
Chalcones
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11814Références
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