Hypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak PARP inhibitory activity
| Autor: | Takashi Mori, Julia Van Steenberg, Jeffrey P. Gius, Masahiro Iwayama, Mami Murakami, Cathy Su, Alexis H. Haskins, Takamitsu A. Kato, Kazuki Heishima, Chisato Omata, Kohji Maruo |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell Survival Science CHO Cells Synthetic lethality Poly(ADP-ribose) Polymerase Inhibitors Pharmacology Depsides Article Carnosol 03 medical and health sciences chemistry.chemical_compound Cricetulus 0302 clinical medicine Cricetinae Animals Gallic acid Cytotoxicity IC50 BRCA2 Protein Multidisciplinary Plant Extracts Chinese hamster ovary cell Carnosic acid Rosmarinus In vitro 030104 developmental biology chemistry Biochemistry Cinnamates 030220 oncology & carcinogenesis Abietanes Medicine Poly(ADP-ribose) Polymerases DNA Damage |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-8 (2017) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Rosemary extract is used in food additives and traditional medicine and has been observed to contain anti-tumor activity. In this study, rosemary extract is hypothesized to induce synthetic lethality in BRCA2 deficient cells by PARP inhibition. Chinese hamster lung V79 cells and its mutant cell lines, V-C8 (BRCA2 deficient) and V-C8 with BRCA2 gene correction were used. Rosemary extract and its major constituent chemicals were tested for their cytotoxicity by colony formation assay in cells of different BRCA2 status. The latter chemicals were tested for inhibitory effect of poly (ADP-ribose) polymerase (PARP) activity in vitro and in vivo. Rosemary has shown selective cytotoxicity against V-C8 cells (IC50 17 µg/ml) compared to V79 cells (IC50 26 µg/ml). Among tested chemicals, gallic acid and carnosic acid showed selective cytotoxicity to V-C8 cells along with PARP inhibitory effects. Carnosol showed comparative PARP inhibitory effects at 100 µM compared to carnosic acid and gallic acid, but the selective cytotoxicity was not observed. In conclusion, we predict that within rosemary extract two specific constituent components; gallic acid and carnosic acid were the cause for the synthetic lethality. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|