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Carnosic Acid Induces Apoptosis Through Reactive Oxygen Species-mediated Endoplasmic Reticulum Stress Induction in Human Renal Carcinoma Caki Cells
| Content Provider | Semantic Scholar |
|---|---|
| Author | Min, Kyoung-Jin Jung, Kyong-Jin Kwon, Taeg Kyu |
| Copyright Year | 2014 |
| Abstract | BACKGROUND Carnosic acid, which is one of extract components of rosemary, has anti-inflammatory, anti-oxidant, and anti-cancer effects. However, the anti-cancer effect of carnosic acid in human renal carcinoma cells is unknown. METHODS Flow cytometry analysis was used to examine the effects of carnosic acid on apoptosis, and Asp-Glu-Val-Asp-ase activity assay kit was used to investigate the involvement of caspase activation. To determine protein expression of apoptotic and endoplasmic reticulum (ER) stress-related proteins, we used Western blotting. Intracellular accumulation of reactive oxygen species (ROS) was determined using the fluorescent probes 2', 7'-dichlorodihydrofluorescein diacetate (H2DCFDA). RESULTS Carnosic acid induced sub-diploid DNA content, sub-G1, population and poly (ADP-ribose) polymerase (PARP) cleavage and activated caspase-3. A pan-caspase inhibitor, a benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone, markedly reduced apoptosis in carnosic acid-treated cells. Carnosic acid promoted intracellular ROS production, and pretreatment with the ROS scavengers (N-acetyl-L-cysteine and glutathione ethyl ester) inhibited carnosic acid-induced apoptosis. Furthermore, carnosic acid also induced expression of ER stress marker proteins, including activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-homologous protein (CHOP), in a dose- and time-dependent manner. Down-regulation of ATF4 and CHOP by small interfering RNA (siRNA) markedly reduced carnosic acid-induced sub-G1 population and PARP cleavage. In addition, carnosic acid induced apoptosis in human breast carcinoma MDA-MB-361 and human hepatocellular carcinoma SK-HEP1 cells, but not in normal human skin fibroblast cells and normal mouse kidney epithelial TMCK-1 cells. CONCLUSION Carnosic acid induced apoptosis through production of ROS and induction of ER stress in human renal carcinoma Caki cells. |
| Starting Page | 170 |
| Ending Page | 178 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| DOI | 10.15430/JCP.2014.19.3.170 |
| PubMed reference number | 25337586 |
| Journal | Medline |
| Volume Number | 19 |
| Alternate Webpage(s) | https://www.e-sciencecentral.org/upload/jcp/pdf/jcp-19-170.pdf |
| Alternate Webpage(s) | https://doi.org/10.15430/JCP.2014.19.3.170 |
| Journal | Journal of cancer prevention |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
