Ursolic acid sensitizes cisplatin-resistant HepG2/DDP cells to cisplatin via inhibiting Nrf2/ARE pathway.
Drug Des Devel Ther
; 10: 3471-3481, 2016.
Article
in En
| MEDLINE
| ID: mdl-27822011
ABSTRACT
BACKGROUND:
Combinations of adjuvant sensitizers with anticancer drugs is a promising new strategy to reverse chemoresistance. Ursolic acid (UA) is one of the natural pentacyclic triterpene compounds known to have many pharmacological characteristics such as anti-inflammatory and anticancer properties. This study investigates whether UA can sensitize hepatocellular carcinoma cells to cisplatin. MATERIALS ANDMETHODS:
Cells were transfected with nuclear factor erythroid-2-related factor 2 (Nrf2) small interfering RNA and Nrf2 complementary DNA by using Lipofectin 2000. The cytotoxicity of cells was investigated by Cell Counting Kit 8 assay. Cell apoptosis, cell cycle, reactive oxygen species, and mitochondrial membrane potential were detected by flow cytometry fluorescence-activated cell sorting. The protein level of Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and heme oxygenase-1 (HO-1) was detected by Western blot analysis.RESULTS:
The results showed that the reverse index was 2.9- and 9.69-fold by UA of 1.125 µg/mL and 2.25 µg/mL, respectively, for cisplatin to HepG2/DDP cells. UA-cisplatin combination induced cell apoptosis and reactive oxygen species, blocked the cell cycle in G0/G1 phase, and reduced the mitochondrial membrane potential. Mechanistically, UA-cisplatin dramatically decreased the expression of Nrf2 and its downstream genes. The sensibilization of UA-cisplatin combination was diminished in Nrf2 small interfering RNA-transfected HepG2/DDP cells, as well as in Nrf2 complementary DNA-transfected HepG2/DDP cells.CONCLUSION:
The results confirmed the sensibilization of UA on HepG2/DDP cells to cisplatin, which was possibly mediated via the Nrf2/antioxidant response element pathway.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Triterpenes
/
Cisplatin
/
Carcinoma, Hepatocellular
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Drug Des Devel Ther
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2016
Document type:
Article