The cytotoxic concentration of rosmarinic acid increases MG132-induced cytotoxicity, proteasome inhibition, autophagy, cellular stresses, and apoptosis in HepG2 cells
Küçük Resim Yok
Tarih
2020
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Sage Publications Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Rosmarinic acid (RA) is a natural polyphenolic compound derived from many common herbal plants. Although it is known that RA has many important biological activities, its effect on proteasome inhibitor-induced changes in cancer treatment or its effects on any experimental proteasome inhibition model is unknown. The aim of the study was to investigate the effect of RA on MG132-induced cytotoxicity, proteasome inhibition, autophagy, cellular stresses, and apoptosis in HepG2 cells. HepG2 cells were treated with 10, 100, and 1000 mu M RA in the presence of MG132 for 24 h; 10 and 100 mu M RA did not affect but 1000 mu M RA decreased cell viability in HepG2 cells. MG132 caused a significant decrease in cell viability and phosphorylation of mammalian target of rapamycin and a significant increase in levels of polyubiquitinated protein, microtubule-associated proteins 1A/1B light chain 3B-II (LC3B-II), heat shock protein 70 (HSP70), binding immunoglobulin protein (BiP), activating transcription factor 4 (ATF4), protein carbonyl, and cleaved poly(adenosine diphosphate-ribose) polymerase 1 (PARP1); 10 and 100 mu M RA did not significantly change these effects of MG132 in HepG2 cells; 1000 mu M RA caused a significant decrease in cell viability and a significant increase in polyubiquitinated protein, LC3B-II, HSP70, BiP, ATF4, protein carbonyl, and cleaved PARP1 levels in MG132-treated cells. Our study showed that only 1000 mu M RA increased MG132-induced cytotoxicity, proteasome inhibition, autophagy, cellular stresses, and apoptosis in HepG2 cells. According to our results, cytotoxic concentration of RA can potentiate the effects of MG132 in hepatocellular carcinoma treatment.
Açıklama
Anahtar Kelimeler
Rosmarinic Acid, Proteasome Inhibitor, Hepatocellular Carcinoma, Autophagy, Oxidative Stress, Apoptosis, Signaling Pathway, Mg132, Degradation, Activation, Line, Prooxidant, Expression, Toxicity, Cleavage, Systems
Kaynak
Human & Experimental Toxicology
WoS Q Değeri
Q4
Scopus Q Değeri
Q2
Cilt
39
Sayı
4
