PUBLICATION
P-glycoprotein modulates oleanolic acid effects in hepatocytes cancer cells and zebrafish embryos
- Authors
- Kayouka, M., Hamade, A., Saliba, E., Najjar, F., Landy, D., Greige-Gerges, H.
- ID
- ZDB-PUB-191111-4
- Date
- 2019
- Source
- Chemico-biological interactions 315: 108892 (Journal)
- Registered Authors
- Hamade, Aline
- Keywords
- Oleanolic acid, P-glycoprotein, Verapamil, Zebrafish
- MeSH Terms
-
- ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism*
- Animals
- Antineoplastic Agents/pharmacology
- Breast Neoplasms/drug therapy
- Breast Neoplasms/metabolism
- Cell Line, Tumor
- Cell Survival/drug effects
- Drug Resistance, Multiple/drug effects
- Drug Resistance, Neoplasm/drug effects
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/metabolism
- Female
- Hep G2 Cells
- Hepatocytes/drug effects*
- Hepatocytes/metabolism
- Humans
- Liver Neoplasms/drug therapy*
- Liver Neoplasms/metabolism
- Oleanolic Acid/pharmacology*
- Verapamil/pharmacology
- Zebrafish/metabolism*
- PubMed
- 31704064 Full text @ Chem. Biol. Interact.
- CTD
- 31704064
Citation
Kayouka, M., Hamade, A., Saliba, E., Najjar, F., Landy, D., Greige-Gerges, H. (2019) P-glycoprotein modulates oleanolic acid effects in hepatocytes cancer cells and zebrafish embryos. Chemico-biological interactions. 315:108892.
Abstract
Oleanolic acid (OA) is a triterpenoid, widely found in plants and possesses antitumor activity in many cancer lines. However, cancer cells develop multidrug resistance (mdr) hindering the effect of anticancer drugs. P-glycoprotein (P-gp) is a major cause of mdr. Therefore, the cytotoxic effect of OA was evaluated on human breast cancer MDA-MB-231 and human liver cancer HepG2 with absence and presence of P-gp, respectively. OA reduced MDA-MB-231 viability in a dose dependent manner, whereas no remarkable effect was observed on HepG2 in the same range of concentrations (1-60 μM). Moreover, cytotoxicity studies were conducted in the presence of verapamil (20 mg/L), a P-gp inhibitor. OA exhibited the same effect on MDA-MB-231 in the absence and presence of verapamil. However, the cytotoxicity was greatly enhanced for HepG2 cells in the presence of verapamil (cell viability dropped from 63.7% to 25% after 72 h at 60 μM). The results were then confirmed in vivo on zebrafish embryos. Increased mortality and malformations were observed in verapamil pretreated group between 5 and 15 μM of OA compared to control; also, all embryos died at 20 μΜ OA and above. These results demonstrate that inhibiting P-gp enhances the chemotherapeutic activity of OA.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping