Trans-chalcone increases p53 activity via DNAJB1/HSP40 induction and CRM1 inhibition.
PLoS One
; 13(8): e0202263, 2018.
Article
in En
| MEDLINE
| ID: mdl-30118500
ABSTRACT
Naturally-occurring chalcones and synthetic chalcone analogues have been demonstrated to have many biological effects, including anti-inflammatory, anti-malarial, anti-fungal, and anti-oxidant/anti-cancerous activities. Compared to other chalcones, trans-chalcone exhibits superior inhibitory activity in cancer cell growth as shown via in vitro assays, and exerts anti-cancerous effects via the activation of the p53 tumor suppressor protein. Thus, characterization of the specific mechanisms, by which trans-chalcone activates p53, can aid development of new chemotherapeutic drugs that can be used individually or synergistically with other drugs. In this report, we found that trans-chalcone modulates many p53 target genes, HSP40 being the most induced gene in the RNA-Seq data using trans-chalcone-treated cells. CRM1 is also inhibited by trans-chalcone, resulting in the accumulation of p53 and other tumor suppressor proteins in the nucleus. Similar effects were seen using trans-chalcone derivatives. Overall, trans-chalcone could provide a strong foundation for the development of chalcone-based anti-cancer drugs.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chalcone
/
Tumor Suppressor Protein p53
/
Receptors, Cytoplasmic and Nuclear
/
Karyopherins
/
HSP40 Heat-Shock Proteins
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2018
Type:
Article
Affiliation country:
Brazil